◀ Back to PIK3R1
IRS2 — PIK3R1
Pathways - manually collected, often from reviews:
-
KEGG Neurotrophin signaling pathway:
IRS1/IRS2/IRS4
→
PIK3CA/PIK3CB/PIK3CD/PIK3CG/PIK3R1/PIK3R2/PIK3R3/PIK3R5
(protein-protein, activation)
-
KEGG Insulin signaling pathway:
IRS1/IRS2/IRS4
→
PIK3CA/PIK3CB/PIK3CD/PIK3CG/PIK3R1/PIK3R2/PIK3R3/PIK3R5
(protein-protein, activation)
-
KEGG Type II diabetes mellitus:
IRS1/IRS2/IRS4
→
PIK3CA/PIK3CB/PIK3CD/PIK3CG/PIK3R1/PIK3R2/PIK3R3/PIK3R5
(protein-protein, activation)
-
KEGG Aldosterone-regulated sodium reabsorption:
IRS1/IRS2/IRS4
→
PIK3CA/PIK3CB/PIK3CD/PIK3CG/PIK3R1/PIK3R2/PIK3R3/PIK3R5
(protein-protein, activation)
-
NCI Pathway Database Signaling events regulated by Ret tyrosine kinase:
IRS2 (IRS2)
→
PI3K complex (PIK3CA-PIK3R1)
(modification, activates)
Hennige et al., Mol Cell Endocrinol 2000, Hayashi et al., Oncogene 2000, Maeda et al., Biochem Biophys Res Commun 2004
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database IL4-mediated signaling events:
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2 complex (IL4-IL4R-JAK1-IL2RG-JAK3-FES-IRS2)
→
PI3K complex (PIK3CA-PIK3R1)
(modification, activates)
Jiang et al., J Immunol 2001, Wurster et al., Mol Cell Biol 2002, Sun et al., Nature 1995, Izuhara et al., Blood 1996
Evidence: mutant phenotype, assay, physical interaction, other species
-
NCI Pathway Database IL2-mediated signaling events:
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/IRS1-2 complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-IRS2_IRS1)
→
PI3K complex (PIK3CA-PIK3R1)
(modification, collaborate)
Johnston et al., J Biol Chem 1995
Evidence: physical interaction
-
NCI Pathway Database IL2-mediated signaling events:
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/IRS1-2 complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-IRS2_IRS1)
→
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/IRS1-2/PI3K complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-IRS2_IRS1-PIK3CA-PIK3R1)
(modification, collaborate)
Johnston et al., J Biol Chem 1995
Evidence: physical interaction
-
NCI Pathway Database IL2-mediated signaling events:
PI3K complex (PIK3CA-PIK3R1)
→
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/IRS1-2/PI3K complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-IRS2_IRS1-PIK3CA-PIK3R1)
(modification, collaborate)
Johnston et al., J Biol Chem 1995
Evidence: physical interaction
-
NCI Pathway Database Signaling events regulated by Ret tyrosine kinase:
IRS2 (IRS2)
→
PI3K complex (PIK3CA-PIK3R1)
(modification, activates)
Hennige et al., Mol Cell Endocrinol 2000, Hayashi et al., Oncogene 2000, Maeda et al., Biochem Biophys Res Commun 2004
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database EPO signaling pathway:
PI3K regualtory subunit polypeptide 1/IRS2/SHIP complex (IRS2-PIK3R1-INPP5D)
→
IRS2 (IRS2)
(modification, collaborate)
Verdier et al., J Biol Chem 1997*
-
NCI Pathway Database EPO signaling pathway:
PI3K regualtory subunit polypeptide 1/IRS2/SHIP complex (IRS2-PIK3R1-INPP5D)
→
SHIP (INPP5D)
(modification, collaborate)
Verdier et al., J Biol Chem 1997*
-
NCI Pathway Database EPO signaling pathway:
PI3K regualtory subunit polypeptide 1/IRS2/SHIP complex (IRS2-PIK3R1-INPP5D)
→
PIK3R1 (PIK3R1)
(modification, collaborate)
Verdier et al., J Biol Chem 1997*
-
NCI Pathway Database EPO signaling pathway:
IRS2 (IRS2)
→
PIK3R1 (PIK3R1)
(modification, collaborate)
Verdier et al., J Biol Chem 1997*
-
Reactome Reaction:
IRS2
→
PIK3R1
(reaction)
-
Reactome Reaction:
IRS2
→
PIK3R1
(indirect_complex)
-
WikiPathways Focal Adhesion-PI3K-Akt-mTOR-signaling pathway:
IRS1/IRS4/IRS2
→
PIK3CA/PIK3R1/PIK3IP1/PIK3R2/PIK3CB/PIK3CD/PIK3R4
(activation)
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
-
IRef Biogrid Interaction:
IRS2
—
PIK3R1
(physical association, affinity chromatography technology)
Tzatsos et al., J Biol Chem 2009*
-
IRef Biogrid Interaction:
IRS2
—
PIK3R1
(physical association, affinity chromatography technology)
Calegari et al., Endocrinology 2005*
-
IRef Biogrid Interaction:
IRS2
—
PIK3R1
(physical association, affinity chromatography technology)
Argetsinger et al., J Biol Chem 1996*
-
IRef Biogrid Interaction:
IRS2
—
PIK3R1
(physical association, affinity chromatography technology)
Verdier et al., J Biol Chem 1997*
-
IRef Biogrid Interaction:
IRS2
—
PIK3R1
(physical association, affinity chromatography technology)
Kim et al., J Biol Chem 1998
-
IRef Biogrid Interaction:
IRS2
—
PIK3R1
(direct interaction, far western blotting)
Hamer et al., Diabetologia 2002*
-
IRef Intact Interaction:
IRS2
—
PIK3R1
(physical association, anti bait coimmunoprecipitation)
Fröjdö et al., Mol Cell Endocrinol 2011*
-
IRef Intact Interaction:
IRS2
—
PIK3R1
(physical association, anti bait coimmunoprecipitation)
Hookham et al., FEBS J 2013*
-
IRef Ophid Interaction:
IRS2
—
PIK3R1
(aggregation, interologs mapping)
Brown et al., Bioinformatics 2005
-
IRef Ophid Interaction:
IRS2
—
PIK3R1
(aggregation, confirmational text mining)
Kim et al., J Biol Chem 1998
Text-mined interactions from Literome
Shaw et al., Mol Cell Biol 2001
(Neoplasm Invasiveness) :
Moreover, we identified a tyrosine residue in the cytoplasmic domain of the beta4 subunit, Y1494, that is required for alpha6beta4 dependent phosphorylation of
IRS-2 and
activation of
PI3K in response to receptor ligation
Richards et al., Endocrinology 2001
:
Collectively, these data suggest that the E2-induced decrease in uterine
insulin receptor substrate-2 requires IGF-I signaling, is not
dependent solely on insulin receptor substrate-1 and
PI3K , and is blocked by progesterone as well as by pharmacological inhibition of proteasomal protease activity
Standaert et al., Endocrinology 2002
:
Presently, in 3T3/L1 adipocytes, rosiglitazone induced sizable increases in basal glucose transport that were : dependent on PI3K, 3-phosphoinositide dependent protein kinase-1 ( PDK-1 ), and PKC-lambda ; accompanied by increases in tyrosine phosphorylation of Cbl and Cbl dependent increases in PI3K and PKC-lambda activity ; but not accompanied by increases in
IRS-1/2 dependent
PI3K or protein kinase B activity ... Additionally, rosiglitazone increased IRS-1 and IRS-2 levels, thereby enhancing insulin effects on IRS-1- and
IRS-2 dependent
PI3K and downstream signaling factors PKC-lambda and protein kinase B
Pirola et al., J Biol Chem 2003
(MAP Kinase Signaling System) :
Conversely, adenoviral-driven expression of constitutively active
PI3K induced an insulin independent reduction in
IRS-1/2 protein levels
Miura et al., Biochemistry 2004
:
Although insulin receptor substrate-1 (IRS-1) and
IRS-2 , among other factors,
activate PI3K , there is little information on the relative roles of IRS-1and IRS-2 during aPKC activation by insulin action in specific cell types ... These findings provide evidence that directly links both IRS-1 and IRS-2 to aPKC activation in immortalized brown adipocytes, and further suggest that IRS-1 and
IRS-2 are
required for the activation of
Cbl/PI3K during insulin action in these cells
Gelling et al., Cell Metab 2006
(Diabetes Mellitus, Experimental) :
Conversely, increased
PI3K signaling
induced by hypothalamic overexpression of either
IRS-2 or protein kinase B ( PKB, a key downstream mediator of PI3K action ) enhanced the glycemic response to insulin by approximately 2-fold in STZ-DM rats
O'Connor et al., J Immunol 2007
(Diabetes Mellitus, Type 2) :
In this study, we report that normal IL-4 dependent elaboration of IL-1 receptor antagonist (IL-1RA) requires
IRS-2 mediated
PI3K activity in primary macrophages
Szabolcs et al., Am J Pathol 2009
(Disease Progression...) :
Because activation of
PI3K signaling
leads to feedback inhibition of
insulin receptor substrate-2 (IRS2) expression, an upstream activator of PI3K, we therefore anticipated that IRS2 expression would be low in tumors that lack PTEN
Aoki et al., Am J Physiol Endocrinol Metab 2009
:
In the livers of p85alpha-deficient mice, p50alpha
played a compensatory role in insulin stimulated
PI3K activation by binding to insulin receptor substrate
(IRS)-1/2
Udelhoven et al., J Endocrinol 2010
:
Thus, alternative binding of ZBP89 or SP1 to the described region in the IRS2 promoter regulates neuronal
IRS2 expression in a
PI3K dependent manner
Kim et al., Endocrinology 1998
(Neuroblastoma) :
We also observed a concomitant increase in the mobility of IRS-2, suggesting that
PI 3-K mediates or is required for IRS-2 serine/threonine phosphorylation, and that this phosphorylation
inhibits IRS-2 tyrosine phosphorylation