◀ Back to INS
INS — INSR
Pathways - manually collected, often from reviews:
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OpenBEL Selventa BEL large corpus:
INSR
→
INS
(directlyIncreases, INS Activity)
Evidence: The insulin receptor belongs to a subfamily of receptor tyrosine kinases that includes the insulin-like growth factor (IGF)-I receptor and the insulin receptor-related receptor (IRR)6.
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BioCarta insulin signaling pathway:
Insulin/Insulin/Insulin Ra/Insulin Ra/Insulin Rb/Insulin Rb complex (INSR-INS)
→
SHC/GRB2/SOS-1 complex (SOS1-GRB2-SHC1)
(modification, activates)
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BioCarta insulin signaling pathway:
Insulin/Insulin/Insulin Ra/Insulin Ra/Insulin Rb/Insulin Rb complex (INSR-INS)
→
IRS-1 (IRS1)
(modification, activates)
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BioCarta insulin signaling pathway:
Insulin/Insulin/Insulin Ra/Insulin Ra/Insulin Rb/Insulin Rb complex (INSR-INS)
→
Insulin Ra/Insulin Ra/Insulin Rb/Insulin Rb complex (INSR)
(modification, collaborate)
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BioCarta insulin signaling pathway:
Insulin/Insulin/Insulin Ra/Insulin Ra/Insulin Rb/Insulin Rb complex (INSR-INS)
→
Insulin (INS)
(modification, collaborate)
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BioCarta insulin signaling pathway:
Insulin Ra/Insulin Ra/Insulin Rb/Insulin Rb complex (INSR)
→
Insulin (INS)
(modification, collaborate)
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BioCarta growth hormone signaling pathway:
Insulin Ra/Insulin Ra/Insulin Rb/Insulin Rb complex (INSR)
→
Insulin (INS)
(modification, collaborate)
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BioCarta growth hormone signaling pathway:
Insulin Ra/Insulin Ra/Insulin Rb/Insulin Rb complex (INSR)
→
Insulin/Insulin Ra/Insulin Ra/Insulin Rb/Insulin Rb complex (INS-INSR)
(modification, collaborate)
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BioCarta growth hormone signaling pathway:
Insulin (INS)
→
Insulin/Insulin Ra/Insulin Ra/Insulin Rb/Insulin Rb complex (INS-INSR)
(modification, collaborate)
-
KEGG Insulin signaling pathway:
INS
→
INSR
(protein-protein, activation)
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KEGG Type II diabetes mellitus:
INS
→
INSR
(protein-protein, activation)
-
KEGG Aldosterone-regulated sodium reabsorption:
INS
→
INSR
(protein-protein, activation)
-
NCI Pathway Database Insulin Pathway:
NCK2 (NCK2)
→
Insulin Receptor/Insulin/IRS1 complex (INSR-INS-IRS1)
(modification, collaborate)
Tu et al., Biochem J 2001*, Lee et al., Proc Natl Acad Sci U S A 1993
Evidence: physical interaction
-
NCI Pathway Database Insulin Pathway:
NCK2 (NCK2)
→
Insulin Receptor/Insulin/IRS1/NCK2 complex (INSR-INS-NCK2-IRS1)
(modification, collaborate)
Tu et al., Biochem J 2001*, Lee et al., Proc Natl Acad Sci U S A 1993
Evidence: physical interaction
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin/IRS1 complex (INSR-INS-IRS1)
→
Insulin Receptor/Insulin/IRS1/NCK2 complex (INSR-INS-NCK2-IRS1)
(modification, collaborate)
Tu et al., Biochem J 2001*, Lee et al., Proc Natl Acad Sci U S A 1993
Evidence: physical interaction
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin/GRB14/PDK1 complex (INSR-INS-GRB14-PDPK1)
→
AKT1 (AKT1)
(modification, activates)
Egawa et al., J Biol Chem 2002, Cross et al., Nature 1995, Alessi et al., EMBO J 1996, Moule et al., J Biol Chem 1997, Cross et al., FEBS Lett 1997
-
NCI Pathway Database Signaling events mediated by TCPTP:
PTP1B (PTPN1)
→
Insulin Receptor/Insulin complex (INSR-INS)
(modification, activates)
Galic et al., Mol Cell Biol 2003*, Meng et al., J Biol Chem 2004*, Galic et al., Mol Cell Biol 2005*
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database Signaling events mediated by TCPTP:
TCPTP p45 (PTPN2)
→
Insulin Receptor/Insulin complex (INSR-INS)
(modification, activates)
Galic et al., Mol Cell Biol 2003*, Meng et al., J Biol Chem 2004*, Galic et al., Mol Cell Biol 2005*
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database Insulin Pathway:
PTP1B (PTPN1)
→
Insulin Receptor/Insulin complex (INSR-INS)
(modification, activates)
Hashimoto et al., J Biol Chem 1992, Hashimoto et al., Biochem J 1992, Kenner et al., J Biol Chem 1993
Evidence: mutant phenotype, assay
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insuli/IRS1/GRB2/SHC complex (INSR-INS-SHC1-GRB2-IRS1)
→
SHC (SHC1)
(modification, collaborate)
Wada et al., Endocrinology 1999, Sharma et al., Mol Endocrinol 2005, Kovacina et al., Biochem Biophys Res Commun 1993, Skolnik et al., Science 1993, Pronk et al., J Biol Chem 1993, Skolnik et al., EMBO J 1993, Ishihara et al., J Biol Chem 1997
Evidence: assay
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insuli/IRS1/GRB2/SHC complex (INSR-INS-SHC1-GRB2-IRS1)
→
GRB2 (GRB2)
(modification, collaborate)
Wada et al., Endocrinology 1999, Sharma et al., Mol Endocrinol 2005, Kovacina et al., Biochem Biophys Res Commun 1993, Skolnik et al., Science 1993, Pronk et al., J Biol Chem 1993, Skolnik et al., EMBO J 1993, Ishihara et al., J Biol Chem 1997
Evidence: assay
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insuli/IRS1/GRB2/SHC complex (INSR-INS-SHC1-GRB2-IRS1)
→
Insulin Receptor/Insulin/IRS1 complex (INSR-INS-IRS1)
(modification, collaborate)
Wada et al., Endocrinology 1999, Sharma et al., Mol Endocrinol 2005, Kovacina et al., Biochem Biophys Res Commun 1993, Skolnik et al., Science 1993, Pronk et al., J Biol Chem 1993, Skolnik et al., EMBO J 1993, Ishihara et al., J Biol Chem 1997
Evidence: assay
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insuli/IRS1/GRB2/SHC complex (INSR-INS-SHC1-GRB2-IRS1)
→
SHIP (INPP5D)
(modification, collaborate)
Wada et al., Endocrinology 1999, Sharma et al., Mol Endocrinol 2005, Kovacina et al., Biochem Biophys Res Commun 1993, Skolnik et al., Science 1993, Pronk et al., J Biol Chem 1993, Skolnik et al., EMBO J 1993, Ishihara et al., J Biol Chem 1997
Evidence: assay
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insuli/IRS1/GRB2/SHC complex (INSR-INS-SHC1-GRB2-IRS1)
→
SHC/SHIP complex (SHC1-INPP5D)
(modification, collaborate)
Wada et al., Endocrinology 1999, Sharma et al., Mol Endocrinol 2005, Kovacina et al., Biochem Biophys Res Commun 1993, Skolnik et al., Science 1993, Pronk et al., J Biol Chem 1993, Skolnik et al., EMBO J 1993, Ishihara et al., J Biol Chem 1997
Evidence: assay
-
NCI Pathway Database Insulin Pathway:
SHC (SHC1)
→
Insulin Receptor/Insulin/IRS1 complex (INSR-INS-IRS1)
(modification, collaborate)
Wada et al., Endocrinology 1999, Sharma et al., Mol Endocrinol 2005, Kovacina et al., Biochem Biophys Res Commun 1993, Skolnik et al., Science 1993, Pronk et al., J Biol Chem 1993, Skolnik et al., EMBO J 1993, Ishihara et al., J Biol Chem 1997
Evidence: assay
-
NCI Pathway Database Insulin Pathway:
GRB2 (GRB2)
→
Insulin Receptor/Insulin/IRS1 complex (INSR-INS-IRS1)
(modification, collaborate)
Wada et al., Endocrinology 1999, Sharma et al., Mol Endocrinol 2005, Kovacina et al., Biochem Biophys Res Commun 1993, Skolnik et al., Science 1993, Pronk et al., J Biol Chem 1993, Skolnik et al., EMBO J 1993, Ishihara et al., J Biol Chem 1997
Evidence: assay
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin/IRS1 complex (INSR-INS-IRS1)
→
SHIP (INPP5D)
(modification, collaborate)
Wada et al., Endocrinology 1999, Sharma et al., Mol Endocrinol 2005, Kovacina et al., Biochem Biophys Res Commun 1993, Skolnik et al., Science 1993, Pronk et al., J Biol Chem 1993, Skolnik et al., EMBO J 1993, Ishihara et al., J Biol Chem 1997
Evidence: assay
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin/IRS1 complex (INSR-INS-IRS1)
→
SHC/SHIP complex (SHC1-INPP5D)
(modification, collaborate)
Wada et al., Endocrinology 1999, Sharma et al., Mol Endocrinol 2005, Kovacina et al., Biochem Biophys Res Commun 1993, Skolnik et al., Science 1993, Pronk et al., J Biol Chem 1993, Skolnik et al., EMBO J 1993, Ishihara et al., J Biol Chem 1997
Evidence: assay
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin/IRS1/Shp2 complex (INSR-INS-PTPN11-IRS1)
→
SHP2 (PTPN11)
(modification, collaborate)
Yamauchi et al., J Biol Chem 1995*
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin/IRS1/Shp2 complex (INSR-INS-PTPN11-IRS1)
→
Insulin Receptor/Insulin/IRS1 complex (INSR-INS-IRS1)
(modification, collaborate)
Yamauchi et al., J Biol Chem 1995*
-
NCI Pathway Database Insulin Pathway:
SHP2 (PTPN11)
→
Insulin Receptor/Insulin/IRS1 complex (INSR-INS-IRS1)
(modification, collaborate)
Yamauchi et al., J Biol Chem 1995*
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos complex (INSR-INS-SHC1-SOS1-GRB2-IRS1)
→
None
(modification, activates)
Mahadev et al., J Biol Chem 2001
Evidence: assay
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin/IRS1 complex (INSR-INS-IRS1)
→
PI3K complex (PIK3CA-PIK3R1)
(modification, activates)
Lavan et al., J Biol Chem 1992*, Hadari et al., J Biol Chem 1992*, Okamoto et al., Biochem J 1993*, Giorgetti et al., J Biol Chem 1993*
Evidence: assay
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin/GRB14/PDK1 complex (INSR-INS-GRB14-PDPK1)
→
AKT2 (AKT2)
(modification, activates)
Egawa et al., J Biol Chem 2002, Cross et al., Nature 1995, Alessi et al., EMBO J 1996, Moule et al., J Biol Chem 1997, Cross et al., FEBS Lett 1997
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin/IRS1 complex (INSR-INS-IRS1)
→
SHIP (INPP5D)
(modification, activates)
Wada et al., Endocrinology 1999
-
NCI Pathway Database Insulin Pathway:
GRB2 (GRB2)
→
Insulin Receptor/Insulin/SHC/GRB2/Sos1 complex (INSR-INS-SHC1-GRB2-SOS1)
(modification, collaborate)
-
NCI Pathway Database Insulin Pathway:
GRB2 (GRB2)
→
Insulin Receptor/Insulin/SHC complex (INSR-INS-SHC1)
(modification, collaborate)
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin/SHC/GRB2/Sos1 complex (INSR-INS-SHC1-GRB2-SOS1)
→
SOS1 (SOS1)
(modification, collaborate)
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin/SHC/GRB2/Sos1 complex (INSR-INS-SHC1-GRB2-SOS1)
→
Insulin Receptor/Insulin/SHC complex (INSR-INS-SHC1)
(modification, collaborate)
-
NCI Pathway Database Insulin Pathway:
SOS1 (SOS1)
→
Insulin Receptor/Insulin/SHC complex (INSR-INS-SHC1)
(modification, collaborate)
-
NCI Pathway Database Insulin Pathway:
IRS1 (IRS1)
→
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B complex (INSR-INS-SHC1-GRB2-PTPN1-IRS1)
(modification, collaborate)
Hashimoto et al., J Biol Chem 1992, Hashimoto et al., Biochem J 1992, Kenner et al., J Biol Chem 1993
-
NCI Pathway Database Insulin Pathway:
IRS1 (IRS1)
→
Insulin Receptor/Insulin complex (INSR-INS)
(modification, collaborate)
Hashimoto et al., J Biol Chem 1992, Hashimoto et al., Biochem J 1992, Kenner et al., J Biol Chem 1993
-
NCI Pathway Database Insulin Pathway:
SHC (SHC1)
→
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B complex (INSR-INS-SHC1-GRB2-PTPN1-IRS1)
(modification, collaborate)
Hashimoto et al., J Biol Chem 1992, Hashimoto et al., Biochem J 1992, Kenner et al., J Biol Chem 1993
-
NCI Pathway Database Insulin Pathway:
SHC (SHC1)
→
Insulin Receptor/Insulin complex (INSR-INS)
(modification, collaborate)
Hashimoto et al., J Biol Chem 1992, Hashimoto et al., Biochem J 1992, Kenner et al., J Biol Chem 1993
-
NCI Pathway Database Insulin Pathway:
GRB2 (GRB2)
→
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B complex (INSR-INS-SHC1-GRB2-PTPN1-IRS1)
(modification, collaborate)
Hashimoto et al., J Biol Chem 1992, Hashimoto et al., Biochem J 1992, Kenner et al., J Biol Chem 1993
-
NCI Pathway Database Insulin Pathway:
GRB2 (GRB2)
→
Insulin Receptor/Insulin complex (INSR-INS)
(modification, collaborate)
Hashimoto et al., J Biol Chem 1992, Hashimoto et al., Biochem J 1992, Kenner et al., J Biol Chem 1993
-
NCI Pathway Database Insulin Pathway:
PTP1B (PTPN1)
→
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B complex (INSR-INS-SHC1-GRB2-PTPN1-IRS1)
(modification, collaborate)
Hashimoto et al., J Biol Chem 1992, Hashimoto et al., Biochem J 1992, Kenner et al., J Biol Chem 1993
-
NCI Pathway Database Insulin Pathway:
PTP1B (PTPN1)
→
Insulin Receptor/Insulin complex (INSR-INS)
(modification, collaborate)
Hashimoto et al., J Biol Chem 1992, Hashimoto et al., Biochem J 1992, Kenner et al., J Biol Chem 1993
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B complex (INSR-INS-SHC1-GRB2-PTPN1-IRS1)
→
Insulin Receptor/Insulin complex (INSR-INS)
(modification, collaborate)
Hashimoto et al., J Biol Chem 1992, Hashimoto et al., Biochem J 1992, Kenner et al., J Biol Chem 1993
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin/SHC complex (INSR-INS-SHC1)
→
Insulin Receptor/Insulin/IRS1 complex (INSR-INS-IRS1)
(modification, collaborate)
Ozes et al., Proc Natl Acad Sci U S A 2001, Yamauchi et al., J Biol Chem 1994, Isakoff et al., J Biol Chem 1996*, Ishihara et al., J Biol Chem 1997
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin/SHC complex (INSR-INS-SHC1)
→
IRS1 (IRS1)
(modification, collaborate)
Ozes et al., Proc Natl Acad Sci U S A 2001, Yamauchi et al., J Biol Chem 1994, Isakoff et al., J Biol Chem 1996*, Ishihara et al., J Biol Chem 1997
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin/SHC complex (INSR-INS-SHC1)
→
Insulin Receptor/Insulin complex (INSR-INS)
(modification, collaborate)
Ozes et al., Proc Natl Acad Sci U S A 2001, Yamauchi et al., J Biol Chem 1994, Isakoff et al., J Biol Chem 1996*, Ishihara et al., J Biol Chem 1997
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin/SHC complex (INSR-INS-SHC1)
→
SHC (SHC1)
(modification, collaborate)
Ozes et al., Proc Natl Acad Sci U S A 2001, Yamauchi et al., J Biol Chem 1994, Isakoff et al., J Biol Chem 1996*, Ishihara et al., J Biol Chem 1997
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin/IRS1 complex (INSR-INS-IRS1)
→
IRS1 (IRS1)
(modification, collaborate)
Ozes et al., Proc Natl Acad Sci U S A 2001, Yamauchi et al., J Biol Chem 1994, Isakoff et al., J Biol Chem 1996*, Ishihara et al., J Biol Chem 1997
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin/IRS1 complex (INSR-INS-IRS1)
→
Insulin Receptor/Insulin complex (INSR-INS)
(modification, collaborate)
Ozes et al., Proc Natl Acad Sci U S A 2001, Yamauchi et al., J Biol Chem 1994, Isakoff et al., J Biol Chem 1996*, Ishihara et al., J Biol Chem 1997
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin/IRS1 complex (INSR-INS-IRS1)
→
SHC (SHC1)
(modification, collaborate)
Ozes et al., Proc Natl Acad Sci U S A 2001, Yamauchi et al., J Biol Chem 1994, Isakoff et al., J Biol Chem 1996*, Ishihara et al., J Biol Chem 1997
-
NCI Pathway Database Insulin Pathway:
IRS1 (IRS1)
→
Insulin Receptor/Insulin complex (INSR-INS)
(modification, collaborate)
Ozes et al., Proc Natl Acad Sci U S A 2001, Yamauchi et al., J Biol Chem 1994, Isakoff et al., J Biol Chem 1996*, Ishihara et al., J Biol Chem 1997
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin complex (INSR-INS)
→
SHC (SHC1)
(modification, collaborate)
Ozes et al., Proc Natl Acad Sci U S A 2001, Yamauchi et al., J Biol Chem 1994, Isakoff et al., J Biol Chem 1996*, Ishihara et al., J Biol Chem 1997
-
NCI Pathway Database Signaling events mediated by PTP1B:
Insulin Receptor/Insulin/SHC complex (INSR-INS-SHC1)
→
Insulin Receptor/Insulin/IRS1 complex (INSR-INS-IRS1)
(modification, collaborate)
Yamauchi et al., J Biol Chem 1994, Isakoff et al., J Biol Chem 1996*, Ishihara et al., J Biol Chem 1997
-
NCI Pathway Database Signaling events mediated by PTP1B:
Insulin Receptor/Insulin/SHC complex (INSR-INS-SHC1)
→
IRS1 (IRS1)
(modification, collaborate)
Yamauchi et al., J Biol Chem 1994, Isakoff et al., J Biol Chem 1996*, Ishihara et al., J Biol Chem 1997
-
NCI Pathway Database Signaling events mediated by PTP1B:
Insulin Receptor/Insulin/SHC complex (INSR-INS-SHC1)
→
Insulin Receptor/Insulin complex (INSR-INS)
(modification, collaborate)
Yamauchi et al., J Biol Chem 1994, Isakoff et al., J Biol Chem 1996*, Ishihara et al., J Biol Chem 1997
-
NCI Pathway Database Signaling events mediated by PTP1B:
Insulin Receptor/Insulin/SHC complex (INSR-INS-SHC1)
→
SHC (SHC1)
(modification, collaborate)
Yamauchi et al., J Biol Chem 1994, Isakoff et al., J Biol Chem 1996*, Ishihara et al., J Biol Chem 1997
-
NCI Pathway Database Signaling events mediated by PTP1B:
Insulin Receptor/Insulin/IRS1 complex (INSR-INS-IRS1)
→
IRS1 (IRS1)
(modification, collaborate)
Yamauchi et al., J Biol Chem 1994, Isakoff et al., J Biol Chem 1996*, Ishihara et al., J Biol Chem 1997
-
NCI Pathway Database Signaling events mediated by PTP1B:
Insulin Receptor/Insulin/IRS1 complex (INSR-INS-IRS1)
→
Insulin Receptor/Insulin complex (INSR-INS)
(modification, collaborate)
Yamauchi et al., J Biol Chem 1994, Isakoff et al., J Biol Chem 1996*, Ishihara et al., J Biol Chem 1997
-
NCI Pathway Database Signaling events mediated by PTP1B:
Insulin Receptor/Insulin/IRS1 complex (INSR-INS-IRS1)
→
SHC (SHC1)
(modification, collaborate)
Yamauchi et al., J Biol Chem 1994, Isakoff et al., J Biol Chem 1996*, Ishihara et al., J Biol Chem 1997
-
NCI Pathway Database Signaling events mediated by PTP1B:
IRS1 (IRS1)
→
Insulin Receptor/Insulin complex (INSR-INS)
(modification, collaborate)
Yamauchi et al., J Biol Chem 1994, Isakoff et al., J Biol Chem 1996*, Ishihara et al., J Biol Chem 1997
-
NCI Pathway Database Signaling events mediated by PTP1B:
Insulin Receptor/Insulin complex (INSR-INS)
→
SHC (SHC1)
(modification, collaborate)
Yamauchi et al., J Biol Chem 1994, Isakoff et al., J Biol Chem 1996*, Ishihara et al., J Biol Chem 1997
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin/IRS3 complex (INSR-INS)
→
Insulin Receptor/Insulin complex (INSR-INS)
(modification, collaborate)
Xu et al., J Biol Chem 1999*
Evidence: assay, physical interaction, other species
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin/SHC/GRB2/Sos1 complex (INSR-INS-SHC1-GRB2-SOS1)
→
HRAS/GTP complex (HRAS)
(modification, activates)
Wick et al., J Biol Chem 2001, Ouwens et al., J Biol Chem 1994, Yamauchi et al., J Biol Chem 1994, Pronk et al., Mol Cell Biol 1994, Sasaoka et al., J Biol Chem 1994
Evidence: assay
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin/SHC/GRB2/Sos1 complex (INSR-INS-SHC1-GRB2-SOS1)
→
HRAS/GDP complex (HRAS)
(modification, activates)
Wick et al., J Biol Chem 2001, Ouwens et al., J Biol Chem 1994, Yamauchi et al., J Biol Chem 1994, Pronk et al., Mol Cell Biol 1994, Sasaoka et al., J Biol Chem 1994
Evidence: assay
-
NCI Pathway Database Insulin Pathway:
GRB10 (GRB10)
→
Insulin Receptor/Insulin/SHC complex (INSR-INS-SHC1)
(modification, collaborate)
O'Neill et al., J Biol Chem 1996, Dong et al., Mol Endocrinol 1997*
Evidence: physical interaction
-
NCI Pathway Database Insulin Pathway:
GRB10 (GRB10)
→
Insulin Receptor/Insulin/SHC/GRB10 complex (INSR-INS-SHC1-GRB10)
(modification, collaborate)
O'Neill et al., J Biol Chem 1996, Dong et al., Mol Endocrinol 1997*
Evidence: physical interaction
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin/SHC complex (INSR-INS-SHC1)
→
Insulin Receptor/Insulin/SHC/GRB10 complex (INSR-INS-SHC1-GRB10)
(modification, collaborate)
O'Neill et al., J Biol Chem 1996, Dong et al., Mol Endocrinol 1997*
Evidence: physical interaction
-
NCI Pathway Database Signaling events mediated by PTP1B:
PTP1B (PTPN1)
→
Insulin Receptor/Insulin complex (INSR-INS)
(modification, inhibits)
Venable et al., J Biol Chem 2000*
Evidence: mutant phenotype, other species
-
NCI Pathway Database Insulin Pathway:
CAP (SORBS1)
→
Insulin Receptor/Insulin/IRS1 complex (INSR-INS-IRS1)
(modification, collaborate)
Baumann et al., Nature 2000, Liu et al., Mol Cell Biol 2002, Hu et al., Mol Cell 2003, Ribon et al., Mol Cell Biol 1998
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database Insulin Pathway:
CBL (CBL)
→
Insulin Receptor/Insulin/IRS1 complex (INSR-INS-IRS1)
(modification, collaborate)
Baumann et al., Nature 2000, Liu et al., Mol Cell Biol 2002, Hu et al., Mol Cell 2003, Ribon et al., Mol Cell Biol 1998
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin/IRS1 complex (INSR-INS-IRS1)
→
APS homodimer complex (SH2B2)
(modification, activates)
Baumann et al., Nature 2000, Liu et al., Mol Cell Biol 2002, Hu et al., Mol Cell 2003, Ribon et al., Mol Cell Biol 1998
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos complex (INSR-INS-SHC1-SOS1-GRB2-IRS1)
→
SOS1 (SOS1)
(modification, collaborate)
Pronk et al., Mol Cell Biol 1994
Evidence: assay, physical interaction
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos complex (INSR-INS-SHC1-SOS1-GRB2-IRS1)
→
Insulin Receptor/Insuli/IRS1/GRB2/SHC complex (INSR-INS-SHC1-GRB2-IRS1)
(modification, collaborate)
Pronk et al., Mol Cell Biol 1994
Evidence: assay, physical interaction
-
NCI Pathway Database Insulin Pathway:
SOS1 (SOS1)
→
Insulin Receptor/Insuli/IRS1/GRB2/SHC complex (INSR-INS-SHC1-GRB2-IRS1)
(modification, collaborate)
Pronk et al., Mol Cell Biol 1994
Evidence: assay, physical interaction
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin/SHC/GRB10 complex (INSR-INS-SHC1-GRB10)
→
p62DOK (DOK1)
(modification, inhibits)
Wick et al., J Biol Chem 2001
Evidence: assay
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin/SHC/GRB10 complex (INSR-INS-SHC1-GRB10)
→
Insulin Receptor/Insulin/SHC/GRB2/Sos1 complex (INSR-INS-SHC1-GRB2-SOS1)
(modification, inhibits)
Wick et al., J Biol Chem 2001
Evidence: assay
-
NCI Pathway Database Insulin Pathway:
LRP (PTPRA)
→
Insulin Receptor/Insulin complex (INSR-INS)
(modification, activates)
Hashimoto et al., J Biol Chem 1992, Hashimoto et al., Biochem J 1992, Kenner et al., J Biol Chem 1993
Evidence: mutant phenotype, assay
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin/GRB14/PDK1 complex (INSR-INS-GRB14-PDPK1)
→
SGK1 (SGK1)
(modification, activates)
Perrotti et al., J Biol Chem 2001*
Evidence: mutant phenotype, assay
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin/GRB14/PDK1 complex (INSR-INS-GRB14-PDPK1)
→
None
(modification, activates)
Perrotti et al., J Biol Chem 2001*
Evidence: mutant phenotype, assay
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor complex (INSR)
→
Insulin Receptor/Insulin complex (INSR-INS)
(modification, collaborate)
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor complex (INSR)
→
Insulin (INS)
(modification, collaborate)
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin complex (INSR-INS)
→
Insulin (INS)
(modification, collaborate)
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin/IRS3 complex (INSR-INS)
→
PI3K complex (PIK3CA-PIK3R1)
(modification, activates)
Xu et al., J Biol Chem 1999*
Evidence: assay, other species
-
NCI Pathway Database Insulin Pathway:
PTP1B (PTPN1)
→
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B complex (INSR-INS-SHC1-GRB2-PTPN1-IRS1)
(modification, collaborate)
Goldstein et al., J Biol Chem 2000, Dadke et al., J Biol Chem 2000, Seely et al., Diabetes 1996, Bandyopadhyay et al., J Biol Chem 1997
Evidence: mutant phenotype, assay
-
NCI Pathway Database Insulin Pathway:
PTP1B (PTPN1)
→
Insulin Receptor/Insuli/IRS1/GRB2/SHC complex (INSR-INS-SHC1-GRB2-IRS1)
(modification, collaborate)
Goldstein et al., J Biol Chem 2000, Dadke et al., J Biol Chem 2000, Seely et al., Diabetes 1996, Bandyopadhyay et al., J Biol Chem 1997
Evidence: mutant phenotype, assay
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B complex (INSR-INS-SHC1-GRB2-PTPN1-IRS1)
→
Insulin Receptor/Insuli/IRS1/GRB2/SHC complex (INSR-INS-SHC1-GRB2-IRS1)
(modification, collaborate)
Goldstein et al., J Biol Chem 2000, Dadke et al., J Biol Chem 2000, Seely et al., Diabetes 1996, Bandyopadhyay et al., J Biol Chem 1997
Evidence: mutant phenotype, assay
-
NCI Pathway Database Signaling events mediated by PTP1B:
NOX4 (NOX4)
→
Insulin Receptor/Insulin complex (INSR-INS)
(modification, activates)
Mahadev et al., Mol Cell Biol 2004*
Evidence: mutant phenotype, assay, other species
-
NCI Pathway Database Signaling events mediated by PTP1B:
Insulin Receptor/Insulin complex (INSR-INS)
(modification, activates)
Mahadev et al., Mol Cell Biol 2004*
Evidence: mutant phenotype, assay, other species
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos complex (INSR-INS-SHC1-SOS1-GRB2-IRS1)
→
HRAS/GTP complex (HRAS)
(modification, activates)
Wada et al., Endocrinology 1999, Sharma et al., Mol Endocrinol 2005, Pronk et al., Mol Cell Biol 1994, Sasaoka et al., J Biol Chem 1994, Myers et al., Mol Cell Biol 1994
Evidence: assay
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos complex (INSR-INS-SHC1-SOS1-GRB2-IRS1)
→
SHC/SHIP complex (SHC1-INPP5D)
(modification, activates)
Wada et al., Endocrinology 1999, Sharma et al., Mol Endocrinol 2005, Pronk et al., Mol Cell Biol 1994, Sasaoka et al., J Biol Chem 1994, Myers et al., Mol Cell Biol 1994
Evidence: assay
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos complex (INSR-INS-SHC1-SOS1-GRB2-IRS1)
→
HRAS/GDP complex (HRAS)
(modification, activates)
Wada et al., Endocrinology 1999, Sharma et al., Mol Endocrinol 2005, Pronk et al., Mol Cell Biol 1994, Sasaoka et al., J Biol Chem 1994, Myers et al., Mol Cell Biol 1994
Evidence: assay
-
NCI Pathway Database Signaling events mediated by PTP1B:
PTP1B (PTPN1)
→
Insulin Receptor/Insulin complex (INSR-INS)
(modification, activates)
Elchebly et al., Science 1999*, Ravichandran et al., Mol Endocrinol 2001
Evidence: mutant phenotype, assay, physical interaction, other species
-
NCI Pathway Database Signaling events mediated by PTP1B:
PTP1B/AKT1 complex (PTPN1-AKT1)
→
Insulin Receptor/Insulin complex (INSR-INS)
(modification, inhibits)
Elchebly et al., Science 1999*, Ravichandran et al., Mol Endocrinol 2001
Evidence: mutant phenotype, assay, physical interaction, other species
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin/GRB14/PDK1 complex (INSR-INS-GRB14-PDPK1)
→
PDK1 (PDPK1)
(modification, collaborate)
King et al., J Biol Chem 2004*
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin/GRB14/PDK1 complex (INSR-INS-GRB14-PDPK1)
→
GRB14 (GRB14)
(modification, collaborate)
King et al., J Biol Chem 2004*
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database Insulin Pathway:
Insulin Receptor/Insulin/GRB14/PDK1 complex (INSR-INS-GRB14-PDPK1)
→
Insulin Receptor/Insulin complex (INSR-INS)
(modification, collaborate)
King et al., J Biol Chem 2004*
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database Insulin Pathway:
PDK1 (PDPK1)
→
Insulin Receptor/Insulin complex (INSR-INS)
(modification, collaborate)
King et al., J Biol Chem 2004*
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database Insulin Pathway:
GRB14 (GRB14)
→
Insulin Receptor/Insulin complex (INSR-INS)
(modification, collaborate)
King et al., J Biol Chem 2004*
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database Insulin-mediated glucose transport:
PP1-C (PPP1CC)
→
Insulin Receptor/Insulin complex (INSR-INS)
(modification, collaborate)
Hubbard et al., Trends Biochem Sci 1993*
-
NCI Pathway Database Insulin-mediated glucose transport:
PP-1G (PPP1R3A)
→
Insulin Receptor/Insulin complex (INSR-INS)
(modification, collaborate)
Hubbard et al., Trends Biochem Sci 1993*
-
Reactome Reaction:
INSR
→
INS
(indirect_complex)
Van Obberghen et al., Eur J Clin Invest 2001*, Bevan et al., Trends Endocrinol Metab 1996*, Cheatham et al., Endocr Rev 1995*, Kahn et al., Diabetes 1994*, White et al., J Biol Chem 1994*, Kandror et al., Am J Physiol 1996*, Di Guglielmo et al., Mol Cell Biochem 1998*
-
Reactome Reaction:
INSR
→
INS
(reaction)
Van Obberghen et al., Eur J Clin Invest 2001*, Bouzakri et al., Cell Metab 2006, Duckworth et al., Endocr Rev 1988*, Cheatham et al., Endocr Rev 1995*, Kahn et al., Diabetes 1994*, White et al., J Biol Chem 1994*, Authier et al., FEBS Lett 1996*, Duckworth et al., Endocr Rev 1998*
-
WikiPathways Focal Adhesion-PI3K-Akt-mTOR-signaling pathway:
EFNA1/FGF1/FGF11/FGF10/EFNA2/EGF/FGF12/CSF1/ANGPT4/ANGPT2/ANGPT1/VEGFA/EFNA3/EFNA4/EFNA5/FGF14/FGF19/FGF17/FGF18/FGF2/FGF3/FGF4/FGF6/FGF7/FGF8/FGF9/FIGF/HGF/IGF1/INS/INS/KITLG/VEGFC/VEGFB/PDGFB/PGF/PDGFA/NGF/PDGFC/FGF21/FGF22/PDGFD/FGF20/FGF16
→
FGFR2/KDR/INSR/FGFR3/IGF1R/KIT/FGFR1/EPHA2/EGFR/CSF1R/FGFR4/FLT1/FLT4/NGFR/MET/PDGFRA/PDGFRB/TEK
(activation)
-
WikiPathways Type II diabetes mellitus:
INS
→
INSR
(activation)
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
Text-mined interactions from Literome
Aspinwall et al., J Biol Chem 1999
:
The presence of a positive feedback mechanism for
insulin secretion
mediated by the
insulin receptor provides a potential link between impaired insulin secretion and insulin resistance
Wang et al., Endocrinology 1999
(Diabetes Mellitus, Experimental) :
Insulin rapidly
stimulated tyrosine phosphorylation of the
insulin receptor , insulin receptor substrate-1 (IRS-1) and, to a lesser extent, IRS-2 in normal and diabetic myocardium
Kole et al., J Basic Clin Physiol Pharmacol 1998
(Insulin Resistance) :
As a result, control and McA4B/LAR cells showed comparable steady-state levels of
insulin receptor phosphorylation in the
presence of
insulin
de L A Fernandes et al., Brain Res 1999
:
Insulin induces tyrosine phosphorylation of the
insulin receptor and SHC, and SHC/GRB2 association in cerebellum but not in forebrain cortex of rats
Hotamisligil et al., Exp Clin Endocrinol Diabetes 1999
(Insulin Resistance...) :
However, we found an approximately 2-fold increase in
insulin stimulated tyrosine phosphorylation of the
insulin receptor in the muscle and adipose tissue of TNF-alpha knockout mice, suggesting that insulin receptor signalling is an important target for TNF-alpha
Sakoda et al., Diabetes 1999
(Diabetes Mellitus, Experimental...) :
However,
insulin induced tyrosine phosphorylation of the
insulin receptor and insulin receptor substrate 1, activation of phosphatidylinositol 3-kinase, and glucose uptake were not affected by PC-1 overexpression
Zhou et al., Mol Cell Biochem 1999
(Obesity) :
In vivo
insulin induced tyrosine phosphorylation of
insulin receptor and insulin receptor substrate-1 was depressed by 82 % ( p < 0.05 ) and 86 % ( p < 0.05 ), respectively
Schechter et al., Neurosci Lett 1999
:
After 2 days in G3 medium the astrocytes were stimulated with 5 ng/ml of insulin for 2 min, and
insulin effects on
insulin receptor , insulin receptor substrate-1 (IRS-1) and ERK-1 and 2 were studied using Western blots ...
Insulin inhibited the phosphorylation of the
insulin receptor and IRS-1 and decreased the activity of the ERK-1, and inhibited the activation of the ERK-2
Jiang et al., J Clin Invest 1999
(Insulin Resistance...) :
Insulin induced tyrosine phosphorylation of
insulin receptor substrates 1 and 2 ( IRS-1 and IRS-2 ) and their protein levels were decreased in the aorta of obese rats compared with lean rats
Friedman et al., Diabetes 1999
(Diabetes Mellitus...) :
The maximal
effect of
insulin on tyrosine phosphorylation of the
insulin receptor was 37 % lower ( P < 0.05 ) in GDM subjects than in pregnant control subjects and was not related to changes in the abundance of the insulin receptor
Wang et al., Mol Cell Biochem 1999
:
These data together indicate that the selective mitogenic
effect of
insulin on CSV3-1 cells involves increased tyrosine phosphorylation of the
insulin receptor , the insulin receptor substrate-1 and the 73 kDa protein, although the underlying mechanisms need to be further elucidated
Wiernsperger et al., Drugs 1999
(Diabetes Mellitus, Type 2) :
Metformin improves insulin sensitivity by increasing
insulin mediated
insulin receptor tyrosine kinase activity, which activates post-receptor insulin signalling pathways
Storz et al., FEBS Lett 1999
(Rhabdomyosarcoma) :
Blocking
insulin signalling by HNMPA- ( AM ) ( 3 ), an
insulin receptor kinase
inhibitor , resulted in the loss of insulin induced STAT5b tyrosine phosphorylation, whereas the inhibition of JAK2 by the JAK selective inhibitor tyrphostin AG490 had no effect
Goldfine et al., Metabolism 2000
(Diabetes Mellitus, Type 2) :
In muscle obtained during clamp studies prior to vanadium therapy,
insulin stimulated the tyrosine phosphorylation of the
insulin receptor , insulin receptor substrate-1 (IRS-1), and Shc proteins by 2- to 3-fold, while phosphatidylinositol 3-kinase ( PI 3-kinase ) activity associated with IRS-1 increased 4.7-fold during insulin stimulation ( P = .02 ) ... Following vanadium, there was a consistent trend for increased basal levels of
insulin receptor , Shc, and IRS-1 protein tyrosine phosphorylation and IRS-1 associated PI 3-kinase, but no further
increase with
insulin
Vincent et al., J Nutr 2000
:
The oligopeptide chromodulin binds chromic ions in response to an insulin mediated chromic ion flux, and the metal saturated oligopeptide can bind to an
insulin stimulated
insulin receptor , activating the receptor 's tyrosine kinase activity
Wang et al., J Biol Chem 2000
(Insulin Resistance) :
Furthermore,
insulin stimulated
insulin receptor and Akt Ser ( 473 ) phosphorylation and phosphatidylinositol 3-kinase activity were 1.6-2.5-fold greater in skeletal muscle from C/EBPbeta ( -/- ) mice compared with WT mice
Meléndez et al., J Cell Biochem 2000
:
Transfected cells had higher levels of insulin binding than that of CHONeoB cells ;
insulin induced phosphorylation of the
insulin receptor and its intracellular substrates were impaired in CHOK1018A cells ... These data indicate that the
insulin receptor with intact kinase activity is
required for
insulin stimulation of g33 mRNA levels
Motoshima et al., Diabetes Res Clin Pract 2000
:
In 32D cells that expressed BK2R and insulin receptor ( 32D-BKR/IR ), bradykinin alone had no effect on the phosphorylation of the insulin receptor, but it enhanced
insulin stimulated tyrosine phosphorylation of the
insulin receptor ... In 32D cells that expressed BK2R, insulin receptor and IRS-1 ( 32D-BKR/IR/IRS1 ), bradykinin also enhanced
insulin stimulated tyrosine phosphorylation of the
insulin receptor and IRS-1
Dean et al., Acta Physiol Scand 2000
(Body Weight) :
Calorie restriction increases
insulin stimulated tyrosine phosphorylation of
insulin receptor and insulin receptor substrate-1 in rat skeletal muscle
Schütt et al., Eur J Endocrinol 2000
:
The
effect of in situ
insulin-stimulation on
insulin receptor kinase activity was studied in Chinese hamster ovary cells with overexpressed human Ser ( 1200 ) -mutated, non mutated, and ATP binding site mutated ( Lys -- > Arg ( 1030 ) ) receptors using a microwell based assay that only detects human ( and not hamster ) insulin receptors ... Although
insulin stimulated kinase activity of human-specific
anti-insulin receptor antibody binding receptors in cells with Ser ( 1200 ) -mutated insulin receptors represented only 3.3 % of that reached in cells with non mutated receptors, a clear insulin induced increase in kinase activity was observed ( 3.4-fold ; P < 0.05 )
Jensen et al., J Biol Chem 2000
:
Subsequent basal and
insulin induced phosphorylation of the
insulin receptor , IRS-1, MAPK, Akt kinase, and GSK-3 were similar in control and pretreated cells
Xu et al., Biochemistry 2000
:
Insulin gene transcription was
stimulated by
insulin receptor signaling and insulin mimetic compound ( L-783 281 ) in a glucose- and Grb2 dependent manner
Sandu et al., Diabetes 2000
(Diabetes Mellitus, Type 2) :
Although GK diabetes did not affect
insulin stimulated tyrosine phosphorylation of the
insulin receptor or its content, insulin stimulated insulin receptor substrate (IRS)-1 tyrosine phosphorylation was severely impaired
Egawa et al., J Biol Chem 2001
(Carcinoma, Hepatocellular...) :
In both cells, PTP1B overexpression blocked
insulin stimulated tyrosine phosphorylation of the
insulin receptor and IRS-1 by more than 70 % and resulted in a significant inhibition of the association between IRS-1 and the p85 subunit of phosphatidylinositol 3-kinase and Akt phosphorylation as well as mitogen activated protein kinase phosphorylation
Vajna et al., Eur J Biochem 2001
(Insulinoma) :
Furthermore, in INS-1 cells, glucose- and KCl induced
insulin release are
reduced by
SNX-482 in a dose dependent manner leading to the conclusion that alpha1E, in addition to L-type and non-L-type ( alpha1A mediated ) Ca2+ currents, is involved in Ca2+ dependent insulin secretion of INS-1 cells
Hirose et al., Metabolism 2001
(Insulin Resistance) :
Insulin stimulated tyrosine phosphorylation of
insulin receptor was reduced to 36 % ( P < .005 ), as was the phosphorylation of IRS-1 to 34 % ( P < .0001 ) of control
Hemming et al., Biochem Cell Biol 2001
:
The
insulin stimulated interaction between hGrb14 and the
insulin receptor was also observed in different mammalian cultured cell lines
Rocha et al., Curr Eye Res 2000
(Diabetes Mellitus, Experimental) :
The
activation of
insulin receptors following insulin treatment, and the involvement of
insulin receptor substrates-1 and -2, Shc, JAK-2 and STAT-1, were analyzed by immunoprecipitation, followed by SDS-PAGE and immunoblotting of rat lacrimal and salivary glands after exposure to insulin ... Functional studies demonstrated that
insulin induced a dose dependent phosphorylation of the
insulin receptor , IGF-1R, insulin receptor substrates-1 and -2, Shc, and STAT-1 ... In rats with streptozotocin induced diabetes mellitus there was a significant reduction in
insulin induced
insulin receptor and STAT-1 phosphorylation in the lacrimal gland but not in the salivary gland ; there was no influence on Shc phosphorylation in either tissue
Braiman et al., Mol Endocrinol 2001
:
Insulin induces specific interaction between
insulin receptor and protein kinase C delta in primary cultured skeletal muscle
Stella et al., Neuroreport 2001
(Ion Channel Gating) :
An
insulin receptor-specific tyrosine kinase inhibitor, HNMPA- ( AM ) 3 ( 50 microM ),
prevented insulin ( 30 nM ) from reducing the depolarization evoked Ca2+ increase in rods
Clodfelder et al., J Biol Inorg Chem 2001
:
The chromium binding oligopeptide chromodulin ( also known as low-molecular-weight chromium binding substance ) has been shown to activate the tyrosine kinase activity of the
insulin receptor in
response to
insulin and has been proposed to be part of a novel autoamplification mechanism for insulin signaling
Watson et al., J Cell Biol 2001
:
Recent studies indicate that
insulin stimulation of glucose transporter (GLUT)4 translocation requires at least two distinct
insulin receptor mediated signals : one leading to the activation of phosphatidylinositol 3 (PI-3) kinase and the other to the activation of the small GTP binding protein TC10
Sweeney et al., Endocrinology 2001
:
Preincubation of cells with leptin also had no effect on
insulin stimulated tyrosine phosphorylation of
insulin receptor , IRS-1 and IRS-2, phosphatidylinositol 3-kinase activity, or Akt phosphorylation
Pelegrinelli et al., J Invest Dermatol 2001
:
It was also observed that acute stimulation with
insulin can
induce tyrosyl phosphorylation of
insulin receptor , that the insulin receptor substrates and Shc proteins serve as signaling molecules for insulin in skin of rats, and that insulin is able to induce association of insulin receptor substrate 1/phosphatidylinositol 3 kinase and Shc/growth-factor-receptor bound protein 2 in this tissue, as well as phosphorylation of mitogen activated protein kinase and serine-threonine kinase, demonstrating that proteins involved in early steps of insulin action are expressed in skin of intact rats and are quickly activated after insulin stimulation
Tagami et al., J Biol Chem 2002
(Insulin Resistance) :
Moreover, when the adipocytes were incubated with exogenous GM3, suppression of tyrosine phosphorylation of
insulin receptor and IRS-1 and glucose uptake in
response to
insulin stimulation was observed, demonstrating that GM3 itself is able to mimic the effects of TNF on insulin signaling
Nakae et al., Endocr Rev 2001
(Growth Disorders) :
Insulin receptor mediates prenatal growth in response to IGF-II and postnatal metabolism in
response to
insulin
Persaud et al., FEBS Lett 2002
:
Insulin receptor activation
inhibits insulin secretion from human islets of Langerhans
Jacob et al., Mol Cell Endocrinol 2002
:
However,
insulin regulation of transfected plasmids
required the expression of cotransfected
insulin receptor
Fernandes et al., Endocrine 2001
:
However,
insulin induced tyrosine phosphorylation of the
insulin receptor and SHC, and the association of SHC/growth factor receptor binding protein-2 ( GRB2 ) decreased significantly from d 1 to wk 60 of life in both types of tissues
Sun et al., J Biol Chem 2002
(Hyperinsulinism) :
Insulin stimulated phosphorylation of the
insulin receptor , insulin receptor substrate (IRS)-1, and associated phosphatidylinositol 3-kinase were normal in TG mice, whereas IRS-2 protein and phosphorylation were down-regulated compared with control mice
Pillutla et al., J Biol Chem 2002
:
Some Site 1 peptides were able to activate the tyrosine kinase activity of the insulin receptor and act as agonists in the insulin dependent fat cell assay, suggesting that Site 1 marks the hotspot involved in
insulin induced activation of the
insulin receptor
Bifulco et al., J Biol Chem 2002
(Hemangioma) :
In contrast, at 25 mm glucose ( HG ), proliferation and thymidine incorporation were stimulated by insulin, serum, epidermal growth factor, and insulin-like growth factor 1 to a comparable extent, whereas basal levels were 25 % lower than those in LG. HG culturing also enhanced
insulin stimulated
insulin receptor and insulin receptor substrate 1 (IRS1) tyrosine phosphorylations while decreasing basal phosphorylations ... Antisense inhibition of SHP-2 reverted the effect of HG on basal and
insulin stimulated
insulin receptor and IRS1 phosphorylation as well as that on thymidine incorporation
Tomazic et al., Diabetologia 2002
(Diabetes Mellitus, Type 2...) :
This study aimed to examine the
effects of
insulin on glucose transport and changes in
insulin receptor tyrosine phosphorylation, IRS-1 and PC-1
Liljebris et al., Bioorg Med Chem 2002
(Insulin Resistance) :
Selective analogues in the series were analyzed in an in vitro cellular assay, which showed increased
insulin stimulated
insulin receptor phosphorylation
Hers et al., Biochem J 2002
:
Here we show that stimulation by
insulin of freshly isolated primary adipocytes
resulted in the expected rapid tyrosine phosphorylation of the
insulin receptor , IRS-1 and IRS-3 ... Furthermore,
insulin induced insulin receptor tyrosine phosphorylation, phosphorylation of Tyr ( 1158 ) and
insulin receptor tyrosine kinase activity were all reduced by inhibition of PI 3-kinase at later time points ( > or=20 min )
Kraus et al., J Endocrinol 2002
:
Furthermore, it correlated with a 35 % reduction in
insulin stimulated
insulin receptor kinase activity after acute leptin pretreatment
Kumar et al., J Exp Biol 2002
(Insulin Resistance) :
We demonstrated that gliclazide enhanced
insulin stimulated
insulin receptor tyrosine phosphorylation in insulin-resistant skeletal muscle cells
Borge et al., Diabetes 2002
:
Studies with transgenic models have shown that the beta-cell-selective
insulin receptor knockout and the IRS-1 knockout
lead to reduced glucose induced
insulin secretion
Tremblay et al., Diabetes 2003
(Obesity) :
Insulin induced tyrosine phosphorylation of the
insulin receptor and insulin receptor substrate (IRS) proteins were similar in muscle of chow- and high-fat fed rats regardless of the dietary protein source
Miki et al., Kobe J Med Sci 2002
:
Glucosamine had no effect on the
insulin stimulated tyrosine phosphorylation of the
insulin receptor and insulin receptor substrate (IRS)-1
Niswender et al., Diabetes 2003
(Anorexia...) :
Here, we report that
insulin induces tyrosine phosphorylation of the
insulin receptor and IRS-1 and -2, increases binding of activated IRS-1 and -2 to the regulatory subunit of PI3K, and activates protein kinase B/Akt, a downstream target of PI3K
Ursø et al., Cell Signal 2003
(Lymphoma, T-Cell) :
Insulin stimulated phosphorylation of the
insulin receptor and of a 160-kDa protein, identified as the IRS-4 protein
Hua et al., Genes Dev 2003
:
Although lacking classical receptor binding determinants,
INS-6 binds to and
activates the human
insulin receptor
Stefan et al., Diabetes 2003
(Diabetes Mellitus...) :
Insulin receptor substrate (IRS)-2 plays an important role in
insulin signaling and its disruption results in diabetes in mice
Bifulco et al., Gynecol Endocrinol 2003
(Choriocarcinoma...) :
However, vanadate treatment reverted the effect of high glucose on basal and
insulin stimulated
insulin receptor and IRS1 phosphorylation
Miyazaki et al., Diabetes 2003
(Diabetes Mellitus, Type 2...) :
RSG therapy had no effect on basal or
insulin stimulated
insulin receptor tyrosine phosphorylation but increased insulin stimulation of IRS-1 tyrosine phosphorylation ( 1.13 +/- 0.11 to 1.56 +/- 0.17 density units ; P < 0.01 vs. prerosiglitazone ) and p85 association with IRS-1 ( 1.00 +/- 0.06 to 1.27 +/- 0.07 activity units ; P < 0.05 vs. prerosiglitazone )
Sampaio de Freitas et al., Biochim Biophys Acta 2003
(Body Weight...) :
In addition, glucose uptake,
insulin receptor substrate 1 (IRS-1) phosphorylation and glucose transporter 4 (GLUT-4) translocation in muscle were reduced in
response to
insulin during suckling
Rafaeloff et al., Biochem Biophys Res Commun 1992
(Liver Neoplasms, Experimental) :
This study suggests, therefore, that charge interactions between
insulin and its receptor may
play a role in
insulin receptor binding and action
Gupta et al., Neurochem Int 1992
(Diabetes Mellitus, Experimental) :
Insulin receptor activity was assessed by [ 125I ] insulin binding, and basal as well as
insulin stimulated kinase activity of the receptor, expressed as phosphorylation of the synthetic peptide poly ( Glu-Tyr ( 4 : 1 ) )
Kahn et al., J Am Soc Nephrol 1992
(Hypertension...) :
Insulin stimulates tyrosine phosphorylation of the
insulin receptor and of an endogenous substrate of approximately 185 kd ( insulin receptor substrate 1 or IRS-1 ) in most cell types
Uhles et al., J Cell Biol 2003
:
Here we show that
activation of the
insulin promoter via A-type and of the glucokinase promoter via B-type
insulin receptor is not dependent on receptor isoform-specific differences in internalization but on the different localization of the receptor types in the plasma membrane
Kushner et al., Diabetes 2004
(Diabetes Mellitus, Type 1) :
Insulin signals are
mediated by tyrosine phosphorylation of the
insulin receptor and its downstream targets, such as Irs1 and Irs2
Denley et al., Horm Metab Res 2003
(Diabetes Mellitus...) :
Activation of the exon 11-
insulin receptor by IGF-II and
insulin results in mitogenic effects and a potentiation of the cancer phenotype
Le et al., Biochem Biophys Res Commun 2004
(Body Weight) :
Kinetics and extents of
insulin stimulated
insulin receptor and IRS-1 tyrosine phosphorylation were similar in wild-type and PTPalpha ( -/- ) liver, muscle, and adipose tissue
Pérez et al., Diabetes 2004
:
However, at elevated concentrations, leptin impaired
insulin stimulated MAPK activity, glycogen synthase kinase (GSK)3beta phosphorylation, and
insulin receptor tyrosine phosphorylation without altering vanadate stimulation
Asilmaz et al., J Clin Invest 2004
(Disease Models, Animal...) :
Leptin treatment at this dose improved
insulin stimulated
insulin receptor and insulin receptor substrate 2 (IRS-2) phosphorylation, IRS-2 associated PI3K activity, and Akt activity in liver
Moeschel et al., J Biol Chem 2004
:
Moreover, we found that the previously described
insulin stimulated , PKC-zeta mediated inhibition of the interaction of IRS-1 with the
insulin receptor and the reduced tyrosine phosphorylation of IRS-1 was abrogated by mutation of IRS-1 Ser ( 318 ) to alanine
Araujo et al., J Endocrinol 2004
(Protein Deficiency) :
Exogenous
insulin stimulation of isolated islets
promoted higher
insulin receptor and IRS-1 and -2 tyrosine phosphorylation in islets from protein-deficient rats, as compared with controls
Kashyap et al., Am J Physiol Endocrinol Metab 2004
(Diabetes Mellitus, Type 2) :
LIP in CON reduced insulin stimulated glucose disposal ( Rd ) by 25 %,
insulin stimulated
insulin receptor tyrosine phosphorylation by 17 %, phosphatidylinositol 3-kinase activity associated with insulin receptor substrate-1 by 20 %, and insulin stimulated glycogen synthase fractional velocity over baseline ( 44 vs. 15 % ; all P < 0.05 )
Rajala et al., Biochemistry 2004
:
We also used retinal organ cultures to demonstrate
insulin activation of the
insulin receptor and subsequent binding of p85, measured through GST pull-down assays with p85 fusion proteins
Göransson et al., J Nutr Biochem 2004
:
Insulin induced tyrosine phosphorylation of the
insulin receptor was not affected by DMAP
Karlsson et al., Eur J Biochem 2004
:
Insulin stimulated phosphorylation of the
insulin receptor and IRS1 was not affected, indicating that caveolae integrity is required downstream of IRS1
Kondo et al., J Biol Chem 2004
(Diabetes Mellitus, Experimental...) :
In streptozotocin mice, in both retina and liver,
insulin receptor (IR) and insulin receptor substrate (IRS)-2 protein and tyrosine phosphorylation were
increased by
insulin , while IRS-1 protein and its phosphorylation were maintained
Xu et al., Biochemistry 2004
(Diabetes Mellitus) :
How
insulin binds to and
activates the
insulin receptor has long been the subject of speculation
Zhu et al., Exp Gerontol 2004
(Body Weight) :
Long-term CR rats exhibited significantly higher
insulin stimulated
insulin receptor tyrosine phosphorylation and lower PTP-1B activity both in liver and skeletal muscle than those observed in rats fed ad libitum ( AL )
Balbis et al., J Biol Chem 2004
:
However, at this concentration, methyl-beta-cyclodextrin perturbed CMD of hepatocyte PM and inhibited insulin induced Akt activation and glycogen synthesis but did not affect
insulin induced
insulin receptor kinase tyrosine phosphorylation
Shi et al., J Biochem 2004
:
However, dansylcadaverine did not affect the
insulin stimulated association of PTP1BC/S with
insulin receptor , as well as dephosphorylation of insulin receptor by PTP1B
Sugita et al., Hypertension 2004
(Insulin Resistance) :
Insulin stimulated tyrosine phosphorylation of
insulin receptor and IRS-1 in SHR was decreased to 55 % ( P < 0.01 ) and 40 % ( P < 0.01 ) of the levels in Wistar-Kyoto rats ( WKY ), respectively
Duan et al., Mol Cell Biol 2004
(Glucose Intolerance...) :
Insulin regulates glucose homeostasis by binding and activating the
insulin receptor , and defects in insulin responses ( insulin resistance ) induce type 2 diabetes ... SH2-B, an Src homology 2 (SH2) and pleckstrin homology domain containing adaptor protein, binds via its SH2 domain to
insulin receptor in
response to
insulin ; however, its physiological role remains unclear
Calegari et al., Endocrinology 2005
:
The inhibition of SOCS-3 expression by a phosphorthioate modified antisense oligonucleotide partially restores angiotensin II-induced inhibition of
insulin induced
insulin receptor , IRS-1 and IRS-2 tyrosine phosphorylation, and IRS-1 and IRS-2 association with p85-phosphatidylinositol 3-kinase and [ Ser473 ] phosphorylation of Akt
Hyun et al., J Nutr 2004
(Diabetes Mellitus, Type 2...) :
Fibroin did not prevent the
insulin induced downregulation of the
insulin receptor or the tyrosine kinase activity associated with the receptor
Bazuine et al., Biochem Biophys Res Commun 2005
:
We observed that pre-treatment with genistein did not affect
insulin induced tyrosine kinase activity of the
insulin receptor or activation of protein kinase B
Morisco et al., Circ Res 2005
(Insulin Resistance) :
On the other hand, long-term stimulation of beta-adrenergic receptors inhibits both
insulin stimulated glucose uptake and insulin induced autophosphorylation of the insulin receptor, and at the same time
promotes threonine phosphorylation of the
insulin receptor
Wharton et al., J Biol Chem 2005
:
Likewise, we determined that
insulin dependent
insulin receptor and IRS1 tyrosine phosphorylation was not significantly different in the four cell lines representing parental, low, medium, and high levels of caveolin-1 expression
Zmora et al., Exp Lung Res 1992
:
High glucose and
insulin levels thus
result in down-regulation of fetal lung insulin receptors and
insulin receptor tyrosine kinase activity late in gestation
Issad et al., Biochimie 2005
:
These results strongly suggest that PTP1B not only dephosphorylates the
insulin receptor that has been
activated by
insulin , but also regulates the insulin receptor precursor during its biosynthesis
Paulus et al., Neuropsychobiology 2005
:
Central nervous
effects of leptin and
insulin on hippocampal leptin and
insulin receptor expression following a learning task in Wistar rats
Pender et al., Metabolism 2005
(Insulin Resistance...) :
Analysis of
insulin stimulated
insulin receptor activation and glucose transport in cultured skeletal muscle cells from obese subjects
Wu et al., Antioxid Redox Signal 2005
(Hyperglycemia) :
Phosphorylation of the
insulin receptor , IRS-1, and Akt in
response to
insulin was also significantly enhanced in high glucose conditions, especially at submaximal insulin concentrations
Paxton et al., Mol Cell Biochem 2005
:
The
insulin receptor tyrosine kinase activity was
stimulated by
insulin , Mg2+ ( half-maximum response at approximately 5.6-10.6 nM and approximately 8.5 mM, respectively ) and by the physiological polyamines, spermine and spermidine
He et al., Mol Endocrinol 2006
(Insulin Resistance) :
IL-1alpha treatment up to 4 h did not alter
insulin stimulated
insulin receptor tyrosine phosphorylation, whereas tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and the association with phosphatidylinositol 3-kinase were partially inhibited with the maximal inhibition in around 15 min. IRS-1 was transiently phosphorylated on some serine residues around 15 min after IL-1alpha stimulation, when several serine kinases, IkappaB kinase, c-Jun-N-terminal kinase, ERK, and p70S6K were activated
Fang et al., Diabetologia 2005
(Insulin Resistance) :
It also showed elevated expression of insulin receptor beta, insulin receptor tyrosine phosphorylation, peroxisome proliferator activated receptor gamma, protein tyrosine phosphatase 1B and phosphorylation of the transcription factor c-Jun, associated with a reduced fold increase of
insulin stimulated
insulin receptor tyrosine phosphorylation in sucrose fed mice
Oriente et al., J Biol Chem 2005
:
14-3-3epsilon overexpression also increased
insulin stimulated
insulin receptor and IRS-1 tyrosine phosphorylation, followed by increased activation of Raf1, ERK1/2, and Akt/protein kinase B
Nagira et al., Endocrinology 2006
(Second Messenger Systems) :
Treatment with 17beta-estradiol ( E2 ) did not affect
insulin induced tyrosine phosphorylation of
insulin receptor
Freude et al., Diabetes 2005
(Diabetes Mellitus, Type 2...) :
Peripheral
insulin stimulation rapidly
increased insulin receptor tyrosine phosphorylation, mitogen activated protein kinase and phosphatidylinositol (PI) 3-kinase pathway activation, and dose dependent tau phosphorylation at Ser202 in the central nervous system
Stanley et al., J Biol Chem 1992
(Pituitary Neoplasms) :
Insulin stimulation of prolactin-chloramphenicol acetyltransferase constructs
requires cotransfection with a human
insulin receptor expression vector
Kellerer et al., Biochem J 1991
:
Furthermore, binding of GTP to these plasma membranes inhibited both the binding of 125I-insulin to the insulin receptor and the stimulation of the insulin receptor kinase, suggesting a feedback interaction between the
insulin stimulated GTP binding site and the
insulin receptor
Moller et al., J Biol Chem 1991
:
We conclude that 1 ) transfected kinase-deficient
insulin receptor mutants derived from insulin-resistant patients have distinct defects in the ability to mediate insulin action in vitro ; 2 ) divergence of insulin signaling pathways may occur at the level of the receptor ; and 3 ) normal activation of the receptor tyrosine kinase by
insulin is not necessarily
required for signaling of certain important biologic actions
Yang et al., J Biochem 2006
:
No inhibition of
insulin induced tyrosine phosphorylation of
insulin receptor and insulin-receptor substrate-1 was observed
Sztalryd et al., J Clin Invest 1991
:
However, both maximal insulin receptor tyrosine kinase activity and
insulin stimulated phosphorylation of the
insulin receptor were significantly lower ( P less than 0.05 ) in cells cultured from the SC region
Dong et al., Diabetologia 2006
(Insulin Resistance) :
Western blot analysis indicated that sucrose feeding : ( 1 ) inhibited
insulin stimulated phosphorylation of
insulin receptor and Akt; (2) enhanced protein-tyrosine phosphatase 1B (PTP1B) expression ; and ( 3 ) suppressed endothelial nitric oxide synthase (eNOS) and Na+-Ca2+ exchanger expression without affecting peroxisome proliferator activated receptor gamma ( PPARgamma ), sarco ( endo ) plasmic reticulum Ca2+-ATPase isozyme 2a and phospholamban
Musi et al., Endocrine 2006
(Diabetes Mellitus, Type 2...) :
Insulin-resistant muscle has defects at several steps of the insulin signaling pathway, including decreases in
insulin stimulated
insulin receptor and insulin receptor substrate-1 tyrosine phosphorylation, and phosphatidylinositol 3-kinase ( PI 3-kinase ) activation ... Weight loss and thiazolidinediones ( TZDs ) improve glucose disposal, in part, by increasing
insulin stimulated
insulin receptor and IRS-1 tyrosine phosphorylation and PI 3-kinase activity
Cho et al., Cell Metab 2006
(Diabetes Mellitus, Type 2...) :
Ectopic expression of PTP-MEG2 in cells inhibited
insulin induced phosphorylation of the
insulin receptor , while RNAi mediated reduction of PTP-MEG2 transcript levels enhanced insulin action
Muñoz et al., J Hypertens 2006
(Disease Models, Animal...) :
We found that in the livers of OZR long-term administration of irbesartan is associated with : ( i ) increased
insulin stimulated
insulin receptor tyrosine phosphorylation ; ( ii ) decreased insulin receptor Ser994 phosphorylation ; ( iii ) augmented insulin receptor substrate (IRS) 1 and 2 abundance and tyrosine phosphorylation ; ( iv ) augmented association between IRS and the p85 regulatory subunit of phosphatidylinositol 3-kinase ; ( v ) increased insulin induced Akt phosphorylation ; and ( vi ) decreased hepatic steatosis
Vera et al., Mol Cell Biol 1990
:
In the
presence of the coexpressed human
insulin receptor ,
insulin induced a two- to threefold increase in hexose transport
Hernández-Valencia et al., Rev Med Inst Mex Seguro Soc 2006
(Diabetes Mellitus, Type 2) :
Phosphorilation of subunit beta from
insulin receptor induced mainly by
insulin , it begins a series of intracellular complex signaling in cascade
Pelletier et al., Mol Cell Biochem 2007
:
While chronic exposure to OHB did not alter
insulin- or vanadate mediated
activation of the
insulin receptor , it suppressed insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation in response to both agonists
Gupta et al., J Cell Biochem 2007
(Insulin Resistance) :
TNF-alpha pre-incubation also showed reduced
insulin stimulated Tyr phosphorylation of
insulin receptor ( IR-beta ) in both the cell types, moreover hyperphosphorylation of IRS-1 at Ser 312 residue was observed in TNF-alpha pre incubated cells
Weedon et al., Diabetes 2006
(Diabetes Mellitus, Type 2...) :
Ectoenzyme nucleotide pyrophosphate phosphodiesterase 1 ( ENPP1 ) is an inhibitor of
insulin induced activation of the
insulin receptor
Leclercq et al., Lab Invest 2007
(Disease Models, Animal...) :
PGZ to MCD fed mice restored the activation of the
insulin receptor and of the Akt pathway in
response to
insulin
Wadley et al., J Appl Physiol 2007
:
Insulin stimulated
insulin receptor and insulin receptor substrate-1 tyrosine phosphorylation were not altered 24 h after acute exercise and short-term training
Kim et al., Pediatr Res 2007
(Insulin Resistance) :
Insulin stimulated phosphorylation of the
insulin receptor was markedly decreased by IGFBP-3 treatment
Cree et al., Ann Surg 2007
(Burns...) :
Tyrosine phosphorylation of the
insulin receptor and insulin receptor substrate-1 in
response to
insulin increased significantly following fenofibrate treatment ( P = 0.04 for both )
Sesti et al., J Endocrinol Invest 1991
:
Although several interpretations are possible, data reported suggest that human
insulin and porcine insulin might differently
affect the
insulin receptor , even if, the biological significance of these findings remains unknown
Denley et al., Mol Cell Biol 2007
:
Differential activation of
insulin receptor substrates 1 and 2 by insulin-like growth factor
activated insulin receptors
Seto-Young et al., J Clin Endocrinol Metab 2007
:
Insulin and TZDs independently
stimulate expression of PPAR-gamma,
insulin receptor , IRS-1, and StAR protein in human ovarian cells
Hee-Park et al., Diabetes Res Clin Pract 2007
:
These results may suggest that the extent of AMPK activation may be a tool for insulin receptors to monitor blood glucose level, with which
insulin induced
insulin receptor activation determines the way to go negatively or positively toward [ Ca ( 2+ ) ] ( c )
Yamauchi et al., Endocrinol Jpn 1991
:
The
effect of phosphorylation of
insulin receptor with adenosine 3',5'-cyclic monophosphate dependent protein kinase ( A kinase ) on its
insulin binding activity was investigated by using insulin receptors prepared from rat liver in vitro
Kavanagh et al., Obesity (Silver Spring) 2007
(Diabetes Mellitus, Type 2...) :
Postprandial insulin and glucose concentrations, and
insulin stimulated serine/threonine protein kinase ( Akt ),
insulin receptor activation, and tumor necrosis factor-alpha concentrations in subcutaneous fat and muscle were measured in subsets of animals
Ruffolo et al., J Biol Chem 2007
(Insulin Resistance) :
Although protein-tyrosine phosphatase 1B (PTP-1B) is a negative regulator of insulin action, adipose tissue from PTP-1B-/- mice does not show enhanced
insulin stimulated
insulin receptor phosphorylation
GarcÃa-San Frutos et al., Endocrinology 2007
(Body Weight...) :
Hypothalamic
insulin stimulated
insulin receptor , GSK3, AKT, and p70S6K phosphorylation decreased with aging
Araújo et al., Endocrinology 2007
(Diabetes Mellitus, Type 2...) :
In addition, the clinical outcomes were accompanied by improved insulin signal transduction in muscle, liver, and hypothalamus, as determined by the evaluation of
insulin induced
insulin receptor , insulin receptor substrate-1, and receptor substrate-2 tyrosine phosphorylation and Akt and forkhead box protein O1 serine phosphorylation
Jensen et al., J Biol Chem 2007
:
Activation of the
insulin receptor by
insulin and a synthetic peptide leads to divergent metabolic and mitogenic signaling and responses
Sridhar et al., Br J Nutr 2008
(Body Weight...) :
High-fat feeding and bitter gourd supplementation did not have any effect on skeletal muscle insulin receptor,
insulin receptor subtrate-1 (IRS-1) and insulin-
stimulated insulin receptor tyrosine phosphorylation compared to chow fed control rats
Perrini et al., Diabetologia 2008
:
Insulin induced phosphorylation of the
insulin receptor , IRS proteins, Akt and extracellular signal regulated kinase-1/2 was more rapid and tended to decrease at earlier time-points in visceral than in subcutaneous adipocytes
Li et al., Rejuvenation Res 2007
:
Although LID mice displayed reduced whole body glucose clearance, cardiomyocytes from LID mice exhibited dramatically enhanced
insulin stimulated phosphorylation of
insulin receptor and Akt
González-Sánchez et al., Clin Endocrinol (Oxf) 2008
(Genetic Predisposition to Disease...) :
Ectonucleotide pyrophosphatase/phosphodiesterase 1 ( ENPP1 ), originally described as a plasma cell allo-antigen and named plasma cell membrane glycoprotein (PC-1), is an inhibitor of
insulin induced activation of the
insulin receptor
MacLaren et al., J Lipid Res 2008
(Insulin Resistance...) :
Insulin receptor and insulin receptor substrate 1 (IRS-1)
increased in the IRO versus pooled
insulin-sensitive ( NO+ISO ) subjects
Yasui et al., J Vasc Res 2008
:
In addition,
insulin enhanced phosphorylation of
insulin receptor , insulin receptor substrate (IRS)-1 and protein kinase B ( Akt ) after 2 min
Li et al., Diabetes 2008
(Hyperhomocysteinemia) :
Hcy impaired glucose transport and, particularly, the insulin signaling pathway as shown by decreased
insulin stimulated tyrosine phosphorylation of
insulin receptor and insulin receptor substrate (IRS)-1, increased serine phosphorylation of IRS-1, and inhibited Akt phosphorylation both in vitro and in vivo, and these impairments were accompanied by an increase in resistin expression
Li et al., J Mol Cell Cardiol 2008
(Cardiomyopathy, Alcoholic...) :
Cardiomyocytes from ethanol fed mice exhibited depressed
insulin stimulated phosphorylation
insulin receptor ( tyr1146 ) and IRS-1 ( tyrosine ) as well as enhanced serine phosphorylation of IRS-1
Papa et al., Trends Endocrinol Metab 1997
:
It is commonly believed that the
insulin receptor mainly
mediates the metabolic effects of
insulin , whereas the closely related IGF-I receptor is considered a major factor for the regulation of cell proliferation
Koschorreck et al., BMC systems biology 2008
:
Hepatic
insulin receptor activation by
insulin binding, receptor internalization and autophosphorylation is explicitly included in the model
Tavaré et al., Biochem J 1991
:
( 2 )
Insulin stimulated
insulin-receptor tyrosine phosphorylation in intact cells was complete within 30 s and was accompanied, after a lag of 2-5 min, by a rise in serine and threonine phosphorylation the beta-subunit ... ( 3 ) Replacement of tyrosine-1162 with phenylalanine blocked
insulin stimulated threonine phosphorylation of the
insulin receptor in intact cells ... ( 5 ) Our data strongly suggest that
insulin stimulated
insulin-receptor serine and threonine phosphorylations are initiated through two distinct pathways, with only the latter showing a strict dependence on autophosphorylation of tyrosine-1162
Whelan et al., J Biol Chem 2008
:
Insulin stimulates purified
insulin receptor to phosphorylate OGT in vitro
Uchigata et al., Diabetes 1991
:
Inducement of antibody that mimics
insulin action on
insulin receptor by insulin autoantibody directed at determinant at asparagine site on human insulin B chain
Ix et al., JAMA 2008
(Diabetes Mellitus...) :
Fetuin-A is a hepatic secretory protein that binds the
insulin receptor and
inhibits insulin action in vitro
Carranza et al., Am J Physiol Cell Physiol 2008
:
At this concentration,
insulin also
increased insulin receptor tyrosine phosphorylation
Kaifu et al., Nephrol Dial Transplant 2009
:
Insulin ( 100 nmol/L )
increased tyrosine phosphorylation of
insulin receptor in peritoneal mesothelial cells
Gu et al., Insect Biochem Mol Biol 2009
:
Phosphorylation of Akt and the
insulin receptor was
stimulated by
insulin , and stimulation of Akt phosphorylation appeared to be PI3K dependent and developmentally regulated
Franklin et al., International journal of clinical and experimental medicine 2008
:
Insulin regulates metabolism and growth in cells of hepatic origin by specifically binding to and activating the tyrosine kinase
insulin receptor
Ku et al., Am J Physiol Cell Physiol 2009
:
EGCG also suppressed
insulin stimulated phosphorylation of the
insulin receptor-beta , insulin receptor (IR) substrates 1 and 2 ( IRS1 and IRS2 ), and mitogen activated protein kinase pathway proteins, RAF1, MEK1/2, and ERK1/2, but not JNK
Tavaré et al., J Biol Chem 1991
:
Insulin promotes
insulin receptor beta-subunit phosphorylation on tyrosine, serine, and threonine residues in a variety of cells, including simian COS cells which transiently express human insulin receptors following transfection with a cDNA encoding the wild-type receptor protein
Kim et al., Proteomics 2009
:
Since the silencing of gC1qR by small RNA interference abolished adipogenesis and blocked
insulin induced activation of
insulin receptor , insulin receptor substrate-1 (IRS-1), Akt, and Erk1/2, we can conclude that gC1qR is an essential molecule involved in adipogenesis and insulin signaling
Zhou et al., Eur J Pharmacol 2009
:
We show in the current study that transient overexpression of PC-1 inhibits
insulin stimulated
insulin receptor tyrosine phosphorylation in HEK293 cells, while knockdown of PC-1 with siRNA significantly increases insulin stimulated Akt phosphorylation in HuH7 human hepatoma cells
Gogg et al., Diabetes 2009
(Diabetes Mellitus, Type 2) :
The expression of insulin receptors was low, but
insulin increased tyrosine phosphorylation of both the
insulin receptor and insulin receptor substrate (IRS)-1 and activated protein kinase B (PKB)
Kwok et al., Diabetes Res 1990
(Diabetes Mellitus, Experimental) :
Insulin induced tyrosine kinase activity of partially purified
insulin receptor measured using poly-glutyr as substrate was also lower in cells from diabetic rats ( normal : 1.4 +/- 0.6-fold ; diabetic 0.5 +/- 0.3-fold above baseline ; ( p less than 0.05 )
Kienesberger et al., J Biol Chem 2009
(Insulin Resistance) :
Insulin stimulated phosphatidylinositol 3-kinase activity and total
insulin receptor and insulin receptor substrate 1, but not other parameters, were also increased in white adipose tissue in vivo
Baillargeon et al., Metab Syndr Relat Disord 2010
(Obesity...) :
This suggests that either obesity or PCOS is associated with a defect in the coupling of the
stimulation of the
insulin receptor by
insulin to the release of the DCI-IPG mediator
Kimura et al., Journal of clinical biochemistry and nutrition 2010
:
Insulin dependent phosphorylation or activation of
insulin receptor , insulin receptor substrate-1 and -2, phosphatidylinositol 3-kinase, Akt and forkhead in rhabdomyosarcoma were not affected by PQ pre-treatment
Shibata et al., J Biol Chem 2010
:
Under these conditions, oxidative stress did not affect
insulin dependent tyrosine phosphorylation of
insulin receptor , insulin receptor substrate (IRS)-1 and -2, or binding of the phosphatidylinositol 3'-OH kinase ( PI 3-kinase ) p85 regulatory subunit or p110alpha catalytic subunit to each IRS
Da Silva et al., Med Sci Sports Exerc 2010
(Inflammation...) :
Our data demonstrated that both protocols of exercise increased insulin sensitivity and increased
insulin stimulated tyrosine phosphorylation of
insulin receptor and insulin receptor substrate 1 and serine phosphorylation of protein kinase B in the muscle of DIO rats by the same magnitude
Piro et al., Endocrinology 2010
:
Insulin stimulated
insulin receptor phosphorylation was greatly reduced by exposure to palmitate
Nov et al., Endocrinology 2010
(Carcinoma, Hepatocellular...) :
CM-TNFalpha treated Fao cells exhibited about 45 % diminution in
insulin stimulated phosphorylation of
insulin receptor , insulin receptor substrate proteins, protein kinase B, and glycogen synthase kinase-3 as compared with CM-treated cells, without changes in the total abundance of these protein
Sugita et al., Mol Cancer Res 2010
(Neoplasm Invasiveness...) :
NO donor inhibited
insulin/IGF-I stimulated phosphorylation of
insulin receptor/IGF-I receptor, IRS-1, Akt/PKB, and glycogen synthase kinase-3beta along with decreased expression of IRS-1 protein in MIAPaCa-2 cells, whereas NO donor enhanced the phosphorylation of extracellular signal regulated kinase-1/2
Sprynski et al., Leukemia 2010
(Multiple Myeloma) :
Insulin is an MGF as potent as IGF-1 at physiological concentrations and requires the presence of insulin/IGF-1 hybrid receptors, stimulating INSR ( + ) IGF-1R ( + ) MMCs, unlike INSR ( + ) IGF-1R ( - ) or INSR ( - ) IGF-1R ( - ) MMCs. Immunoprecipitation experiments indicate that
INSR is linked with IGF-1R in MMCs and that
insulin induces both IGF-1R and INSR phosphorylations and vice versa
Huang et al., J Biol Chem 2010
:
In addition to inhibiting insulin receptor and IGF1R kinase activity by directly binding to the receptors, GRB10 can also negatively
regulate insulin and IGF1 signaling by mediating
insulin receptor and IGF1R degradation through ubiquitination
Barbour et al., J Clin Endocrinol Metab 2011
(Diabetes, Gestational...) :
GDM women had decreased skeletal muscle
insulin stimulated
insulin receptor and insulin receptor substrate 1 (IRS1) tyrosine activation and reduced IRS1, concomitant with increased basal IRS1 serine phosphorylation and basal p70 S6-kinase ( S6K1 ) activation, which resolved postpartum
Saiya-Cork et al., Clin Cancer Res 2011
(Chromosome Deletion...) :
INSR stimulation by
insulin in CLL cells ex vivo resulted in the activation of canonical INSR signaling pathways, including the AKT-mTOR and Ras/Raf/Erk pathways, and INSR activation partially abrogated spontaneous CLL cell apoptosis ex vivo
Huang et al., Am J Hypertens 2011
:
We hypothesize that there is also an interaction between D ( 3 ) dopamine and
insulin receptors, i.e., stimulation of the D ( 3 ) receptor
inhibits insulin receptor expression and function
Weiland et al., Proc Natl Acad Sci U S A 1990
:
In the
presence of
insulin , the agent competitively inhibits insulin stimulated DNA synthesis ( [ 3H ] thymidine incorporation into total DNA ), glucose transport activity ( 2-deoxyglucose uptake rate ), and
insulin receptor tyrosine kinase activity
Magri et al., Biochem J 1990
:
The present study was undertaken to determine the effects of porcine growth hormone ( pGH ) on glucose transport, to establish which lipogenic enzymes were affected by pGH, and to determine if changes in insulin binding or
insulin receptor kinase activity
contributed to the diminished
insulin responsiveness of adipocytes from pigs treated with pGH
Kruszynska et al., Diabetologia 1990
:
Our results support the notion that the
insulin receptor exists in an active an inactive form, and that elevated plasma
insulin concentrations
increases the proportion of active receptors
Clementi et al., Metabolism 2011
(Insulin Resistance) :
Hepatic
insulin dependent
insulin receptor autophosphorylation, Akt activation, and FoxO1 phosphorylation were similar between Lep ( db ) x IL6KO mice and Lep ( db ) controls
Blondel et al., Am J Physiol 1990
(Diabetes Mellitus, Experimental...) :
In wheat germ agglutinin purified receptors, 125I labeled porcine insulin binding, basal and
insulin stimulated
insulin receptor kinase activities for both the autophosphorylation of the beta-subunit and the phosphorylation of the artificial substrate poly ( Glu-Tyr ) 4 : 1, were found identical in diabetic and control rats, treated or not with vanadate
Yamamoto et al., J Clin Endocrinol Metab 1990
(Acanthosis Nigricans...) :
The degree of
insulin dependent autophosphorylation and the tyrosine kinase activity of the
insulin receptor from the patient 's lymphocytes were decreased to 15 % and 13 %, respectively, in a cell-free system
Loh et al., Diabetologia 2012
(Diabetes Mellitus, Type 2...) :
Blood glucose and insulin levels, insulin and glucose tolerance, and
insulin induced muscle
insulin receptor activation and downstream PI3K/Akt signalling remained unaltered in chow fed Mck-Cre ; Ptpn2 ( lox/lox ) versus Ptpn2 ( lox/lox ) mice
Ross et al., Physiol Behav 2012
(Disease Models, Animal...) :
There were no differences between the groups in terms of
insulin stimulated phosphorylation of
insulin receptor ß subunit (IR-ß) and protein kinase B ( PKB/AKT ) in hippocampal slices or hippocampal BDNF or IGF-1 concentrations
Kwon et al., J Biol Chem 2012
:
Piceatannol, natural polyphenolic stilbene, inhibits adipogenesis via modulation of mitotic clonal expansion and
insulin receptor dependent
insulin signaling in early phase of differentiation
Gupta et al., Hypertension 2012
(Disease Models, Animal...) :
Either ouabain or
insulin alone
caused accumulation of and carcinoembryonic antigen cell adhesion molecule, as well as
insulin receptor-ß , and epidermal growth factor receptor in early endosomes, but no synergy was demonstrable
Morcavallo et al., J Biol Chem 2012
:
Insulin and insulin-like growth factor II differentially
regulate endocytic sorting and stability of
insulin receptor isoform A
Chiefari et al., Scientific reports 2012
:
In the present study, we investigated whether
activation of the
INSR by
insulin affected HMGA1 protein phosphorylation and its regulation of gene transcription
Sartorius et al., Cell Physiol Biochem 2012
:
Leptin treatment led to a significant decrease in insulin mediated phosphorylation of the insulin receptor and Akt473 which was accompanied by a decline in glycogen synthesis in primary astrocytes and significantly decreased
insulin induced phosphorylation of the
insulin receptor and insulin receptor substrate-2 in brain tissues of mice
Park et al., Hepatology 2013
(Glucose Intolerance...) :
Conclusion : We conclude that the sphingolipid acyl chain composition of liver
regulates insulin signaling by modifying
insulin receptor translocation into membrane microdomains
Arunkumar et al., Nutr Res 2012
(Insulin Resistance) :
Hyperglycemia and hyperinsulinemia observed in HFFD fed mice were significantly lowered by GEN. GEN increased
insulin stimulated tyrosine phosphorylation of
insulin receptor-ß and insulin receptor substrate (IRS) 1 but down-regulated IRS-1 serine phosphorylation in the skeletal muscle of HFFD fed mice
Macia et al., Diabetes 2012
(Inflammation...) :
Importantly, treatment of adipocytes with the supernatant of activated Y1-deficient macrophages causes insulin resistance, as demonstrated by decreased
insulin induced phosphorylation of the
insulin receptor and Akt as well as decreased expression of insulin receptor substrate 1
Cervelli et al., Stem Cells Transl Med 2012
:
PRP with insulin synergistically upregulated fibroblast growth factor receptor ( FGFR ) and downregulated epidermal growth factor receptor ( ErbB ) expression ; moreover, PRP in association prevented
insulin induced insulin-like growth factor-1 receptor and
insulin receptor downregulation
Ju Ha et al., J Recept Signal Transduct Res 2013
(MAP Kinase Signaling System) :
In the present study, we explored to determine if
insulin receptor could associate with syndecan-1 in
response to
insulin and such association could lead to the activation of subsequent ERK I/II and alkaline phosphatase (ALP) in osteoblast cells ...
Insulin rapidly
induces the association of
insulin receptor with syndecan-1
Ahn et al., J Biol Chem 2013
(Disease Models, Animal...) :
In this study, we found that
insulin directly binds to insulin receptors in Leydig cell membranes and
activates phospho-insulin receptor-ß ( phospho-IR-ß ), phospho-IRS1, and phospho-AKT, leading to up-regulation of DAX-1 ( dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 ) gene expression in the MA-10 mouse Leydig cell line
Bottomley et al., Am J Physiol 1990
(Hyperinsulinism) :
Insulin induced downregulation of the
insulin receptor occurs in conditions associated with high extracellular concentrations of insulin
Caro et al., Metabolism 1989
:
Glyburide 's actions were mediated without altering the following : ( 1 ) 125I-insulin binding ; ( 2 ) the electrophoretic mobility of the affinity labeled alpha-subunit or the autophosphorylated beta-subunit of the insulin receptor ; and ( 3 ) the
insulin stimulated
insulin receptor kinase activity using histone or the beta-subunit of the insulin receptor as phosphoacceptors
Czech et al., Ciba Found Symp 1989
:
Experiments in our laboratory have identified three distinct insulin activated serine kinase activities in cell-free extracts that appear to account for the
insulin stimulated serine phosphorylation of the
insulin receptor itself, ATP citrate lyase, and acetyl CoA carboxylase, respectively
Treadway et al., J Biol Chem 1989
:
Insulin and Mn/MgATP treatment of immunoaffinity purified alpha beta heterodimeric insulin receptors
induced the formation of an alpha 2 beta 2 heterotetrameric
insulin receptor complex
Pang et al., J Biol Chem 1985
(Liver Neoplasms, Experimental) :
These results confirm our notion that
insulin initially
stimulated tyrosine autophosphorylation and subsequently serine phosphorylation of the
insulin receptor in intact cells and suggests that this sequence of reactions occurs faster on receptors that are dephosphorylated before the incubation with insulin
Balage et al., Reprod Nutr Dev 1989
:
The change during fasting of the
insulin stimulated tyrosine kinase activity of the
insulin receptor is specific to certain tissue
Okabayashi et al., Diabetes 1989
(Pancreatic Neoplasms) :
Mechanisms of
insulin induced
insulin-receptor downregulation ... Slot blots and Northern transfers revealed that
insulin induced an approximately 50 % decrease in
insulin-receptor mRNA levels
Obermaier-Kusser et al., J Biol Chem 1989
(Diabetes Mellitus, Type 2) :
Therefore, the reduced formation of the tris phosphorylated regulatory region in the diabetic receptors suggests that a defective autophosphorylation cascade leading to tris-phosphorylation of the regulatory region may cause, in part, the reduced
insulin stimulated kinase activity of the
insulin receptor in muscle of NIDDM patients
Wilden et al., Biochem J 1987
:
Further, in the
presence of
insulin , the
insulin-receptor kinase activity was also observed to be more sensitive to oxidation by H2O2 and FeCl3/ascorbate compared with insulin receptors in the absence of insulin
Tornqvist et al., J Biol Chem 1988
:
Relationship of site-specific beta subunit tyrosine autophosphorylation to
insulin activation of the
insulin receptor ( tyrosine ) protein kinase activity
Cecchin et al., Am J Physiol 1988
(Disease Models, Animal...) :
Furthermore, the ability of
insulin to
stimulate the autophosphorylation of the beta-subunit and
insulin receptor kinase activity using Glu80, Tyr20 as exogenous phosphoacceptor was increased in the liver of the uremic animals
Kergoat et al., Biochem Biophys Res Commun 1988
(Diabetes Mellitus, Type 2) :
Basal and
insulin stimulated
insulin receptor kinase activities were also found normal for both the autophosphorylation of the beta subunit of the insulin receptor and the phosphorylation of the artificial substrate poly ( Glu-Tyr ) 4 : 1
Smith et al., Biochem J 1988
(Liver Neoplasms, Experimental) :
Two systems in vitro are described that show
insulin stimulated phosphorylation of the
insulin receptor on serine residues
Whittaker et al., J Clin Endocrinol Metab 1985
(Cell Transformation, Viral...) :
Insulin stimulated phosphorylation of the
insulin receptor was studied in cultured B-lymphocytes transformed by Epstein-Barr virus
Testa et al., Dev Biol Stand 1985
(Carcinoma, Hepatocellular...) :
Effect of
insulin on an
insulin receptor of PLC/PRF/5 human hepatoma cell line
Grémeaux et al., Am J Physiol 1987
:
Basal and maximally
insulin stimulated
insulin receptor tyrosine kinase activity, tested in a cell-free system, was similar for both autophosphorylation and phosphorylation of exogenous substrates in the absence or in the presence of PMB
Otsu et al., Biochem J 1988
(Chondrosarcoma) :
Because physiological concentrations of insulin do not influence proteoglycan synthesis in non transformed chondrocytes, the findings indicated a possible abnormality in the
insulin dependent regulation of the
insulin receptor in these tumour cells
Hachiya et al., J Biol Chem 1987
:
The additive
effects of PMA and
insulin on
insulin receptor phosphorylation suggest that the phorbol ester and insulin act via independent signaling mechanisms
Poretsky et al., J Clin Endocrinol Metab 1988
:
This possible effect of
insulin on the ovary could be
mediated by either the
insulin receptor or the type I insulin-like growth factor (IGF) receptor, both of which have been described in the human ovary
Tornqvist et al., J Biol Chem 1988
(Liver Neoplasms, Experimental) :
The
insulin stimulated tyrosine phosphorylation of the
insulin receptor in intact rat hepatoma cells thus involves at least 6 of the 13 tyrosine residues located on the beta subunit intracellular extension
Morrison et al., J Biol Chem 1988
:
These data demonstrate that ( i ) insulin treatment can induce the reassociation of the alpha beta heterodimeric complex into a covalent alpha 2 beta 2 heterotetrameric state, and ( ii )
insulin dependent protein kinase activation of the alpha beta heterodimeric
insulin receptor correlates with the covalent reassociation into a disulfide linked alpha 2 beta 2 heterotetrameric complex
Torossian et al., J Biol Chem 1988
:
Vanadate down-regulates cell surface
insulin and growth hormone receptors and
inhibits insulin receptor degradation in cultured human lymphocytes
Maassen et al., Biochim Biophys Acta 1987
:
The
effect of
insulin , serum and dexamethasone on mRNA levels for the
insulin receptor in the human lymphoblastoic cell line IM-9
Hayes et al., Proc Natl Acad Sci U S A 1987
:
These data demonstrate that, under certain conditions, H2O2 stimulates insulin receptor phosphorylation and tyrosine kinase activity, suggesting that the
insulin-like effects of H2O2 may be
mediated by stimulation of
insulin receptor phosphorylation
Chen et al., J Biol Chem 1986
:
We have examined the
insulin dependent phosphorylation of the
insulin receptor in the isolated plasma membranes of 3T3-F442A adipocytes
Devaskar et al., Biochem Biophys Res Commun 1986
(Hyperinsulinism...) :
We conclude that 1 ) regardless of the ability of insulin to cross the blood brain barrier, the downregulation of the brain
insulin receptor is
insulin dose
dependent and 2 ) the downregulation of the fetal brain insulin receptor is not a physiologic but a pharmacologic effect of insulin
Caro et al., J Clin Invest 1986
(Diabetes Mellitus...) :
However,
insulin stimulated
insulin receptor kinase activity was decreased in diabetics
Patsch et al., J Biol Chem 1986
:
Anti-insulin receptor IgG
inhibited binding of porcine
insulin to cells in a dose dependent fashion
McElduff et al., Horm Metab Res 1986
(Hypoglycemia) :
The erythrocyte
insulin receptor response to
insulin induced hypoglycaemia
Sugaya et al., Gastroenterol Jpn 1986
(Liver Neoplasms, Experimental) :
The
effect of
insulin and glucagon on the
insulin receptor of cultured hepatoma cells ... To elucidate the mechanism of glucagon-insulin (G-I) therapy, the
effect of
insulin and/or glucagon on the
insulin receptor was studied in an experiment utilizing cultured cells ( JTC-16 ) of rat ascites hepatoma
Morgan et al., Proc Natl Acad Sci U S A 1987
:
Acute
insulin action
requires insulin receptor kinase activity : introduction of an inhibitory monoclonal antibody into mammalian cells blocks the rapid effects of insulin
Morrison et al., J Biol Chem 1987
:
Comparisons between the time courses of beta subunit autophosphorylation with those of Glu : Tyr phosphorylation both in the presence and absence of insulin confirmed that
insulin can
stimulate the exogenous protein kinase activity of the
insulin receptor in the complete absence of beta subunit autophosphorylation
Skouby et al., Am J Obstet Gynecol 1986
(Pregnancy in Diabetics) :
The effect of a low-dose triphasic oral contraceptive ( ethinyl estradiol and levonorgestrel ) on glucose tolerance, plasma
insulin response to a glucose challenge, and
insulin receptor binding to monocytes and erythrocytes was investigated in seven women with previous gestational diabetes and seven nondiabetic control subjects ... The effect of a low-dose triphasic ( ethinyl estradiol and levonorgestrel ) on glucose tolerance, plasma
insulin response to a glucose challenge, and
insulin receptor binding to monocytes and erythrocytes was investigated in 7 women with previous gestational diabetes and 7 nondiabetic control subjects
Livingston et al., Diabetes 1985
:
The
insulin receptor and its
regulation by
insulin was studied in U-937 monocytes, a human cell line with properties similar to those of normal peripheral blood monocytes
Golden et al., Metabolism 1985
(Diabetes Mellitus, Lipoatrophic...) :
Binding of insulin to IgG, IgM, and IgE was not increased,
insulin binding to monocytes and erythrocytes was not sufficiently abnormal to account for the the insulin resistance, and
insulin receptor increased insulin clearance or accelerated degradation of insulin by tissues
Eckel et al., Basic Res Cardiol 1985
:
The data suggest
involvement of the
insulin receptor in
insulin degradation, which includes internalization and lysosomal processing of insulin
Yorek et al., J Neurochem 1985
(Eye Neoplasms...) :
By contrast, studies with the various brain preparations indicate that the brain
insulin receptor is not
down-regulated by circulating levels of
insulin
Mössner et al., Z Gastroenterol 1985
(Diabetes Mellitus, Experimental...) :
Next the characteristics of the
insulin receptor of exocrine pancreatic acini and its
regulation by
insulin , so called `` up- and downregulation '', are discussed
van Obberghen et al., Biochim Biophys Acta 1979
:
Analysis of the data of binding at steady state indicated that the decrease in binding of 125I labeled
insulin was
due to a reduced affinity of the
insulin receptor without noticeable change in the concentration of receptor sites
Haring et al., Biochemistry 1984
(Liver Neoplasms, Experimental) :
Insulin stimulated phosphorylation of
insulin receptor purified partially on immobilized wheat germ agglutinin
Nissley et al., Clin Endocrinol Metab 1984
:
The original idea that an IGF receptor mediates the growth promoting action of both IGFs and insulin while acute metabolic effects of
insulin and IGFs are
mediated by the
insulin receptor is an oversimplification
Postel-Vinay et al., Exp Cell Res 1983
:
Our results suggest that the cultured chondrocytes possess a common receptor for the somatomedin peptides and that
insulin , which is able to stimulate sulfate incorporation into proteoglycans,
acts through an
insulin receptor distinct from the somatomedin site
Cheng et al., Ann Clin Lab Sci 1984
:
They appear to be formed by limited proteolysis from cell membrane proteins or glycoproteins and act as transmembrane signals following the binding of
insulin to its receptor and the
activation of the
insulin-receptor complex
Ronnett et al., J Biol Chem 1983
:
Insulin induced down-regulation of cellular
insulin receptor level had no effect on the time required for the newly synthesized receptors to reach the cell surface
Zick et al., J Biol Chem 1983
:
Characterization of
insulin mediated phosphorylation of the
insulin receptor in a cell-free system
Van Obberghen et al., Proc Natl Acad Sci U S A 1983
:
In the work reported here, the kinase activity responsible for the
insulin stimulated phosphorylation of the
insulin receptor was localized
Pagano et al., Diabetologia 1983
(Diabetes Mellitus) :
These results show that
insulin receptor binding is diminished in Type 1 diabetes, perhaps as a
consequence of higher peripheral blood
insulin levels and that metformin can improve binding, and so reduce the amount of insulin needed to reach euglycaemia
Plehwe et al., Biochem J 1983
:
Phosphorylation of the
insulin receptor of isolated rat adipocytes in
response to
insulin has been studied
Grigorescu et al., J Biol Chem 1983
:
Insulin binding and
insulin dependent phosphorylation of the
insulin receptor solubilized from human erythrocytes
Bar et al., Biochim Biophys Acta 1984
:
Despite the extensive fatty acyl changes, the lipid modified cells demonstrated no change in the binding of insulin or the insulin-like growth factor, multiplication stimulating activity, and little alteration in
insulin induced down-regulation of the
insulin receptor , or in cell processing of insulin
Takayama et al., Proc Natl Acad Sci U S A 1984
(Liver Neoplasms, Experimental) :
This report shows that phorbol esters stimulate
insulin receptor phosphorylation,
inhibit insulin induced receptor phosphorylation and
insulin action, and suggest a physiologic relation between insulin action and the calcium activated and phospholipid dependent protein kinase C
Iwasaki et al., Horm Metab Res 1982
:
The increase in
insulin binding is
due to increase in affinity of
insulin receptor without changes in the number of insulin receptors
Avruch et al., J Biol Chem 1982
:
Insulin stimulated tyrosine phosphorylation of the
insulin receptor in detergent extracts of human placental membranes
Howard et al., Metabolism 1981
(Diabetes Mellitus, Lipoatrophic) :
Insulin binding, as indicated by maximum specific 125I-insulin binding and concentration of unlabelled insulin for 50 % displacement, was normal, although
insulin regulation of the
insulin receptor was diminished
King et al., J Clin Invest 1980
:
These data demonstrate directly that the
insulin receptor mediates the metabolic effects of
insulin and MSA, whereas the growth promoting action of both peptides is mediated by the MSA receptor or other growth factors
Caro et al., Science 1980
:
Down regulation of the
insulin receptor of primary cultures of rat hepatocytes occurs in the
presence of
insulin and several agents with insulin-like activity, which act through or distal to the insulin receptor
Prince et al., Diabetes 1981
(Diabetes Mellitus) :
Insulin binding, internalization, and
insulin receptor regulation in fibroblasts from type II, non-insulin dependent diabetic subjects
Ronnett et al., J Biol Chem 1982
:
These results indicate that
insulin dependent regulation of
insulin receptor level in 3T3-L1 adipocytes involves a change in the rate of receptor degradation
Fantus et al., J Biol Chem 1982
:
Regulation of the
insulin receptor by
insulin is independent of the steroid effect
Fehmann et al., Digestion 1994
(Glucagonoma) :
When INR1G9 cells were transiently transfected with a hybrid gene containing the promotor/enhancer region of the human insulin receptor promotor ( 1,462 bp ) linked to the transcriptional reporter gene chloramphenicol acetyltransferase and were treated with insulin it was demonstrated that
insulin did not
affect the
insulin receptor gene transcription
Goodyear et al., J Clin Invest 1995
(Obesity) :
In the lean subjects, tyrosine phosphorylation of the
insulin receptor and insulin receptor substrate-1 (IRS-1), measured by immunoblotting with anti-phosphotyrosine antibodies, was significantly
increased by
insulin at all time points
Carter et al., Biochemistry 1995
:
Studies into the identity of the sites of
insulin stimulated
insulin receptor serine phosphorylation ... The identity of the sites of insulin stimulated serine phosphorylation in the human insulin receptor was examined by synthesizing peptides that together encompassed all the serine residues of the cytosolic portion of the beta-subunit and testing them as substrates for phosphorylation by a preparation of human insulin receptor copurified with
insulin stimulated
insulin receptor serine kinase activity ... Two-dimensional thin-layer tryptic mapping of the phosphorylated insulin
receptor/insulin stimulated insulin receptor serine kinase preparation or of
insulin receptor phosphorylated in human Hep G2 cells yielded two major peptides, called S1 and S2, that ran as a pair of closely migrating spots, and other lesser peptides that contained phosphoserine
Harada et al., J Biol Chem 1995
:
10 nM
insulin significantly
increased tyrosine phosphorylation of
insulin receptor and IRS-1 in CHOHIRc cells ... Phosphorylation of
insulin receptor and IRS-1 in CHONEO and CHOA1018K cells was not detected in the
presence or absence of
insulin
Chang et al., J Biol Chem 1995
:
Intravenous
insulin stimulated
insulin receptor tyrosine kinase activity by 7-fold in control muscle versus < or = 1.5-fold in muscle from transgenic mice
Goodyear et al., Am J Physiol 1995
:
Insulin increased tyrosine phosphorylation of the
insulin receptor and IRS-1, whereas contraction alone had no effect
Joost et al., Cell Signal 1995
:
It was long believed that the effects of
insulin are
mediated by a unique
insulin receptor
Zachayus et al., J Cell Physiol 1995
:
Inverse variations were observed between Hsps72,73 synthesis and both cell surface
insulin receptor level and
insulin glycogenic
response in fetal hepatocytes experiencing heat stress
Chuang et al., Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 1994
:
Okadaic acid activated the kinase activity of the
insulin stimulated
insulin receptor , but not the basal activity of the insulin receptor without the addition of insulin
Saad et al., Endocrinology 1995
(Insulin Resistance...) :
Prolonged
insulin treatment
induced a time- and dose dependent decrease in
insulin receptor and IRS-1 protein levels, reaching nadirs of 40 +/- 4 % ( P < 0.01 ) and 15 +/- 6 % ( P < 0.005 ) of control levels, respectively, after 24 h with 100 nM insulin
Chuang et al., J Biol Chem 1994
:
Interactive
roles of Ras,
insulin receptor substrate-1, and proteins with Src homology-2 domains in
insulin signaling in Xenopus oocytes
Levy-Toledano et al., J Biol Chem 1994
:
Subsequent to
insulin stimulated phosphorylation of the
insulin receptor , a complex is formed that contains the insulin receptor and PI 3-kinase
Yamauchi et al., Mol Cell Biol 1994
:
To assess the relative
effects of various
insulin receptor , IRS1, and Grb2 levels on
insulin signaling, parental CHO cells were transiently transfected with various combinations of expression plasmids encoding these proteins
Kim et al., J Cell Physiol 1993
:
Taken together, these results indicate that
insulin rapidly
increases nuclear
insulin receptor appearance and activates nuclear tyrosine kinase activity
Feinstein et al., J Biol Chem 1993
(Liver Neoplasms, Experimental) :
Tumor necrosis factor-alpha suppresses
insulin induced tyrosine phosphorylation of
insulin receptor and its substrates
Flier et al., J Clin Endocrinol Metab 1993
(Acromegaly...) :
This data combined with our previously published epidemiological data concerning the frequency of the Met985 allele, indicate that this variant
insulin receptor is not
responsible for the
insulin resistant glucose uptake or the clinical syndrome of pseudoacromegaly
Ahn et al., J Biol Chem 1993
:
These data suggest that by itself phosphorylation of threonine 1336 has no significant effect on
insulin binding,
regulation of
insulin receptor expression, or insulin signal transduction
Petruzziello et al., J Clin Endocrinol Metab 1993
(Diabetes Mellitus, Type 2) :
We conclude that the Gln1152
insulin receptor impairs
insulin regulation of metabolic responses in patient cells
Russ et al., FEBS Lett 1993
:
In the presence of ATP or AMP-PNP,
insulin significantly
enhanced the binding of [ 35S ] GTP-gamma-S to the partially purified
insulin receptor
Issad et al., Eur J Biochem 1995
:
Isoproterenol inhibits
insulin stimulated tyrosine phosphorylation of the
insulin receptor without increasing its serine/threonine phosphorylation
Santos et al., Diabete Metab 1995
(Diabetes Mellitus, Type 2) :
There was no change in erythrocyte insulin receptor binding associated with metformin treatment, but both basal and
insulin stimulated
insulin receptor tyrosine kinase activities of solubilized erythrocyte insulin receptors were significantly higher after 10 weeks of metformin treatment
Velloso et al., FEBS Lett 1995
:
Glucose- and
insulin induced phosphorylation of the
insulin receptor and its primary substrates IRS-1 and IRS-2 in rat pancreatic islets
Kulas et al., J Biol Chem 1996
(Carcinoma, Hepatocellular) :
Here,
insulin dependent
insulin receptor tyrosine kinase activation was examined with recombinant insulin receptor substrate 1 (IRS-1) as the substrate and shown to be 3-fold greater in cells with suppressed LAR levels
Ito et al., Proc Natl Acad Sci U S A 1996
:
Immobilized
insulin activated the
insulin receptor and downstream signaling proteins, and this activation persisted for longer periods than that obtained with free insulin, probably explaining the greater mitogenic effect of the immobilized insulin
Kole et al., J Biol Chem 1996
:
Moreover, the addition of a N-stearyl derivative of 3S-peptide-I to intact CHO/HIRc cells caused a concentration dependent increase in
insulin stimulated phosphorylation of the
insulin receptor , with a maximum effect ( approximately 2.7-fold ) at 50 microM
Stefan et al., Diabetes 1996
:
We conclude that the reported inhibition of
insulin signaling by PC-1 does not
result from a direct inhibition of the
insulin receptor kinase activity
Zhang et al., Mol Endocrinol 1996
:
In contrast, overexpression of recombinant LAR cytoplasmic domain, detected as a 72-kDa protein in the cell cytosol, did not significantly affect the
insulin stimulated tyrosine phosphorylation of the
insulin receptor or IRS-1 ( 99 % and 93 % of control at 10 min, respectively )
Fan et al., Shock 1996
(Hyperglycemia) :
Endotoxin induced alterations in
insulin stimulated phosphorylation of
insulin receptor , IRS-1, and MAP kinase in skeletal muscle
Carter et al., Biochemistry 1996
:
The kinase could be reconstituted back to the insulin receptor stripped of the kinase to yield a high stoichiometry of serine phosphorylation of the
insulin receptor in the
presence of
insulin ( 0.75 +/- 0.15 mol/mol of beta-subunit, mean +/- SEM, n = 3 ) ... Phosphorylation of serine 1078 of the insulin receptor to high stoichiometry by the kinase did not affect
insulin stimulated exogenous protein tyrosine kinase activity of the
insulin receptor
Asamoah et al., Biochem J 1995
:
Studies on an
insulin stimulated
insulin receptor serine kinase activity : separation of the kinase activity from the insulin receptor and its reconstitution back to the insulin receptor ... Recently we have achieved co-purification of the insulin receptor with
insulin stimulated
insulin receptor serine kinase activity ... The major myelin basic protein serine kinase activity in the NaCl eluate co-purified exactly on Mono Q with the activity that restored
insulin stimulated
insulin receptor serine phosphorylation
Reis et al., J Nutr 1997
(Protein Deficiency...) :
Glucose induced insulin secretion is impaired and
insulin induced phosphorylation of the
insulin receptor and insulin receptor substrate-1 are increased in protein-deficient rats ... Therefore, we conclude that a decreased glucose induced
insulin secretion in pancreatic islets from protein malnourished rats is
responsible , at least in part, for an increased phosphorylation of the
insulin receptor , insulin receptor substrate-1 and its association with phosphatidylinositol 3-kinase
Davis et al., Biochemistry 1997
:
A possible new mechanism for the amplification of
insulin receptor tyrosine kinase activity in
response to
insulin has been identified
Elmendorf et al., Am J Physiol 1997
(Insulin Resistance) :
Despite these differences, denervated soleus and plantaris muscles exhibited comparable decreases in
insulin stimulated activities of the
insulin receptor ( approximately 40 % ) and phosphatidylinositol 3-kinase ( approximately 50 % ) and a pronounced decrease in GLUT-4
Chuang et al., Biochem Biophys Res Commun 1997
(Carcinoma, Hepatocellular) :
These data indicate that
insulin receptor signaling can activate the transcriptional regulatory function of STAT protein, and that
insulin actions on Stat1alpha are
mediated through signaling pathways independent of JAK family of kinases
Hwang et al., Mol Cells 1997
:
Tyrosine phosphorylation of the
insulin receptor and IRS-1 was
increased by
insulin
Kusari et al., Mol Endocrinol 1997
:
MKP-1 mRNA induction by
insulin required
insulin receptor tyrosine kinase activity, since overexpression of an altered insulin receptor with impaired intrinsic tyrosine kinase activity prevented mRNA induction
Ito et al., J Endocrinol 1997
:
The binding of
insulin to its receptor rapidly
induces intrinsic
insulin receptor tyrosine kinase activity, resulting in tyrosine phosphorylation of various cytosolic substrates, such as insulin receptor substrate-1 (IRS-1) which, in turn, associates with a p85 subunit of phosphatidylinositol 3-kinase ( PI 3-kinase ) followed by activation of this enzyme
Kole et al., Indian J Biochem Biophys 1997
:
Furthermore, we found that the introduction of a N-stearyl derivative of 3S-peptide-I in CHO/HIRc cells caused a significant increase in
insulin stimulated phosphorylation of the
insulin receptor
Bortoli et al., Endocrinology 1997
(Carcinoma, Hepatocellular) :
Vanadate, but not
insulin ,
inhibits insulin receptor gene expression in rat hepatoma cells
Carvalho et al., Diabetes 1997
:
The acute administration of bradykinin increased
insulin stimulated tyrosine phosphorylation of the
insulin receptor and IRS-1 in the liver and muscle
Ito et al., Biosci Biotechnol Biochem 1997
(Starvation) :
In intact rat livers, starvation increased the
insulin dependent tyrosine phosphorylation of the
insulin receptor and IRS-1 as has been described by others
Maggi et al., Endocrinology 1998
:
Eventually, the events observed are specific for Cys860, as individual substitution of the two more proximal Cys residues ( 795 and 872 ) to Ser is not accompanied by any change in either
insulin induced
insulin receptor internalization or IRS-1 phosphorylation
Jacob et al., J Biol Chem 1998
:
The negative effect of RPTPalpha on
insulin activation of the prolactin promoter is not
due to reduced phosphorylation or kinase activity of the
insulin receptor or to reduced phosphorylation of insulin receptor substrate-1 or Shc
Valverde et al., Endocrinology 1998
(Insulin Resistance) :
However,
insulin receptor substrate (IRS)-1 and IRS-2 signaling in
response to
insulin showed functional differences
Sasse et al., Braz J Med Biol Res 1997
:
These data demonstrate that after unilateral nephrectomy there is a decrease in
insulin induced
insulin receptor and IRS-1 tyrosine phosphorylation levels in kidney but not in liver and muscle
Nolte et al., Diabetes 1998
:
We found that exposure of soleus muscles to 6 nmol/l TNF-alpha for 45 min in vitro had no inhibitory effect on
insulin stimulated tyrosine phosphorylation of the
insulin receptor or insulin receptor substrate 1 (IRS-1) or on phosphatidylinositol 3-kinase association with IRS-1
Goldfine et al., Mol Cell Biochem 1998
(Diabetes Mellitus, Type 2...) :
Transfection of PC-1 into cultured cells has confirmed that overexpression of PC-1 can produce impairments in
insulin receptor tyrosine kinase activity and the subsequent cellular
responses to
insulin
Brozinick et al., J Biol Chem 1998
:
Studies in muscle and adipose tissue have shown that
insulin induces its receptor dependent phosphorylation of
insulin receptor substrates 1 and 2, which leads to activation of polyphosphatidylinositol (PI) 3'-kinase
Gliozzo et al., J Cell Biochem 1998
(Breast Neoplasms) :
In many human breast cancers and cultured cell lines,
insulin receptor expression is elevated, and
insulin , via its own insulin receptor, can
stimulate cell growth
Hresko et al., J Biol Chem 1998
(Insulin Resistance) :
Analysis of the insulin signaling cascade revealed that glucosamine impaired
insulin receptor autophosphorylation, insulin receptor substrate ( IRS-1 ) phosphorylation, IRS-1 associated PI 3-kinase activity in the LDM, and AKT-1
activation by
insulin
Goalstone et al., J Biol Chem 1998
:
We conclude that the effect of
insulin on FTase is specific,
requires the presence of an intact
insulin receptor , and serves as a conduit for the `` priming '' influence of insulin on the nuclear effects of other growth factors
Sorokin et al., Biochem J 1998
:
Insulin induced tyrosine phosphorylation of
insulin receptor substrates results in the redistribution of CrkII between p130 ( cas ) and insulin receptor substrate-1
Chen et al., Endocrinology 1998
:
Interestingly, we did not observe any major effects of alpha2-HSG to inhibit
insulin stimulated phosphorylation of the
insulin receptor , insulin receptor substrate-1, -2, or -3, in either transfected or freshly isolated adipose cells
Yamamoto et al., J Biol Chem 1998
:
We found that overexpression of caveolin-3 augmented
insulin stimulated phosphorylation of insulin receptor substrate-1 in 293T cells but not the phosphorylation of
insulin receptor
Carvalho et al., Biochem Mol Biol Int 1998
(Obesity) :
Following treatment with captopril there was an improvement in
insulin induced
insulin receptor and pp185 phosphorylation in the liver and muscle of obese rats
Frick et al., Biochem J 1998
:
Studies using a tyrosine kinase inhibitor and introduction into adipocytes of anti-phosphotyrosine or inhibitory anti-insulin receptor beta-subunit antibodies demonstrated dependence on tyrosine phosphorylation but independence of
insulin receptor kinase
activation of the
insulin-mimetic signalling and metabolic activity of the PIG compounds
Short et al., Am J Physiol 1998
(Diabetes Mellitus, Experimental...) :
Gel filtration chromatography, competition of
insulin binding, and
activation of the
insulin receptor kinase activity demonstrated that this mature insulin was functionally identical to that of authentic processed insulin
Storz et al., FEBS Lett 1998
:
TNF downregulated insulin induced
insulin receptor kinase activity and
insulin induced activation of the transcription factor STAT5
Chen et al., Biochemistry 1999
:
Furthermore, the inhibitor blocked the
insulin stimulated association of PTP1B with the
insulin receptor