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GRB2 — PIK3CA

Pathways - manually collected, often from reviews:

• NCI Pathway Database Neurotrophic factor-mediated Trk receptor signaling: SHC/GRB2/SOS1/GAB1/PI3K complex (SHC1-GRB2-SOS1-GAB1-PIK3CA-PIK3R1) → SHC/GRB2/SOS1/GAB1 complex (SHC1-GRB2-SOS1-GAB1) (modification, collaborate)
  Obermeier et al., EMBO J 1993, Cunningham et al., J Biol Chem 1997, Holgado-Madruga et al., Proc Natl Acad Sci U S A 1997
  Evidence: mutant phenotype, physical interaction, other species
• NCI Pathway Database Neurotrophic factor-mediated Trk receptor signaling: SHC/GRB2/SOS1/GAB1/PI3K complex (SHC1-GRB2-SOS1-GAB1-PIK3CA-PIK3R1) → PI3K complex (PIK3CA-PIK3R1) (modification, collaborate)
  Obermeier et al., EMBO J 1993, Cunningham et al., J Biol Chem 1997, Holgado-Madruga et al., Proc Natl Acad Sci U S A 1997
  Evidence: mutant phenotype, physical interaction, other species
• NCI Pathway Database Neurotrophic factor-mediated Trk receptor signaling: SHC/GRB2/SOS1/GAB1 complex (SHC1-GRB2-SOS1-GAB1) → PI3K complex (PIK3CA-PIK3R1) (modification, collaborate)
  Obermeier et al., EMBO J 1993, Cunningham et al., J Biol Chem 1997, Holgado-Madruga et al., Proc Natl Acad Sci U S A 1997
  Evidence: mutant phenotype, physical interaction, other species
• NCI Pathway Database IL2 signaling events mediated by PI3K: None → IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GRB2/SOS1/GAB2/SHP2/PI3K complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SHC1-GRB2-SOS1-GAB2-PTPN11-PIK3CA-PIK3R1) (modification, collaborate)
  Augustine et al., Mol Cell Biol 1991, Gómez et al., J Immunol 1997
  Evidence: assay, other species
• NCI Pathway Database IL2 signaling events mediated by PI3K: IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GRB2/SOS1/GAB2/SHP2/PI3K complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SHC1-GRB2-SOS1-GAB2-PTPN11-PIK3CA-PIK3R1) → PKC zeta (PRKCZ) (modification, activates) Gómez et al., Exp Cell Res 1995, Gómez et al., J Immunol 1997
  Evidence: mutant phenotype, other species
• NCI Pathway Database VEGFR3 signaling in lymphatic endothelium: SHC/GRB2/SOS1 complex (SOS1-GRB2-SHC1) → PI3K complex (PIK3CA-PIK3R1) (modification, activates)
  Mäkinen et al., EMBO J 2001, Salameh et al., Blood 2005
  Evidence: assay
• NCI Pathway Database Signaling events regulated by Ret tyrosine kinase: RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2 complex (RET-GFRA1-GDNF-SHC1-GRB2-GAB1) → 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 SHP2 signaling: IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GRB2/SOS1/GAB2/SHP2/PI3K complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SHC1-GRB2-SOS1-GAB2-PTPN11-PIK3CA-PIK3R1) → PI3K complex (PIK3CA-PIK3R1) (modification, collaborate)
  Gadina et al., J Biol Chem 2000, Gu et al., Mol Cell Biol 2000, Merida et al., J Immunol 1991, Truitt et al., J Biol Chem 1994, Kanazawa et al., Cell Immunol 1994, Gómez et al., J Immunol 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database SHP2 signaling: IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GRB2/SOS1/GAB2/SHP2/PI3K complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SHC1-GRB2-SOS1-GAB2-PTPN11-PIK3CA-PIK3R1) → IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GRB2/SOS1/GAB2/SHP2 complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SHC1-GRB2-SOS1-GAB2-PTPN11) (modification, collaborate)
  Gadina et al., J Biol Chem 2000, Gu et al., Mol Cell Biol 2000, Merida et al., J Immunol 1991, Truitt et al., J Biol Chem 1994, Kanazawa et al., Cell Immunol 1994, Gómez et al., J Immunol 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database SHP2 signaling: PI3K complex (PIK3CA-PIK3R1) → IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GRB2/SOS1/GAB2/SHP2 complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SHC1-GRB2-SOS1-GAB2-PTPN11) (modification, collaborate)
  Gadina et al., J Biol Chem 2000, Gu et al., Mol Cell Biol 2000, Merida et al., J Immunol 1991, Truitt et al., J Biol Chem 1994, Kanazawa et al., Cell Immunol 1994, Gómez et al., J Immunol 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database IL6-mediated signaling events: GRB2/SOS1/GAB family/SHP2/PI3K complex (GRB2-SOS1-GAB1_GAB2-PTPN11-PIK3CA-PIK3R1) → AKT1 (AKT1) (modification, activates) Jee et al., J Invest Dermatol 2002
  Evidence: mutant phenotype
• NCI Pathway Database Signaling events regulated by Ret tyrosine kinase: RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2 complex (RET-GFRA1-GDNF-SHC1-GRB2-GAB1) → 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 Signaling events regulated by Ret tyrosine kinase: RET9/GFRalpha1/GDNF/Shank3/Grb2 complex (RET-SHANK3-GRB2-GFRA1-GDNF) → PI3K complex (PIK3CA-PIK3R1) (modification, activates)
  Schuetz et al., J Cell Biol 2004
  Evidence: mutant phenotype, assay
• NCI Pathway Database GMCSF-mediated signaling events: GMCSF/GMR alpha/CSF2RB/JAK2 (dodecamer)/SHC/GRB2/GAB2 complex (CSF2RB-JAK2-SHC1-GRB2-GAB2-CSF2-CSF2RA) → GMCSF/GMR alpha/CSF2RB/JAK2 (dodecamer)/SHC/GRB2/GAB2/PI3K complex (CSF2RB-JAK2-SHC1-GRB2-GAB2-CSF2-CSF2RA-PIK3CA-PIK3R1) (modification, collaborate)
  Dijkers et al., Oncogene 1999, Gu et al., Mol Cell Biol 2000, Guthridge et al., EMBO J 2006, Sato et al., EMBO J 1993
  Evidence: mutant phenotype, physical interaction
• NCI Pathway Database GMCSF-mediated signaling events: GMCSF/GMR alpha/CSF2RB/JAK2 (dodecamer)/SHC/GRB2/GAB2 complex (CSF2RB-JAK2-SHC1-GRB2-GAB2-CSF2-CSF2RA) → PI3K complex (PIK3CA-PIK3R1) (modification, collaborate)
  Dijkers et al., Oncogene 1999, Gu et al., Mol Cell Biol 2000, Guthridge et al., EMBO J 2006, Sato et al., EMBO J 1993
  Evidence: mutant phenotype, physical interaction
• NCI Pathway Database GMCSF-mediated signaling events: GMCSF/GMR alpha/CSF2RB/JAK2 (dodecamer)/SHC/GRB2/GAB2/PI3K complex (CSF2RB-JAK2-SHC1-GRB2-GAB2-CSF2-CSF2RA-PIK3CA-PIK3R1) → PI3K complex (PIK3CA-PIK3R1) (modification, collaborate)
  Dijkers et al., Oncogene 1999, Gu et al., Mol Cell Biol 2000, Guthridge et al., EMBO J 2006, Sato et al., EMBO J 1993
  Evidence: mutant phenotype, physical interaction
• NCI Pathway Database Trk receptor signaling mediated by PI3K and PLC-gamma: None → SHC/GRB2/SOS1/GAB1/PI3K complex (SHC1-GRB2-SOS1-GAB1-PIK3CA-PIK3R1) (modification, collaborate)
  
• NCI Pathway Database IL2 signaling events mediated by PI3K: None → IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GRB2/SOS1/GAB2/SHP2/PI3K complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SHC1-GRB2-SOS1-GAB2-PTPN11-PIK3CA-PIK3R1) (modification, activates)
  Gu et al., Mol Cell Biol 2000, Lindemann et al., J Biol Chem 2003, Akbar et al., Eur J Immunol 1996, Ahmed et al., Proc Natl Acad Sci U S A 1997, Reif et al., J Biol Chem 1997
  Evidence: mutant phenotype, assay, other species
• NCI Pathway Database IL2-mediated signaling events: IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GRB2/SOS1/GAB2/SHP2/PI3K complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SHC1-GRB2-SOS1-GAB2-PTPN11-PIK3CA-PIK3R1) → PI3K complex (PIK3CA-PIK3R1) (modification, collaborate)
  Gadina et al., J Biol Chem 2000, Gu et al., Mol Cell Biol 2000, Merida et al., J Immunol 1991, Truitt et al., J Biol Chem 1994, Kanazawa et al., Cell Immunol 1994, Gómez et al., J Immunol 1997, Gadina et al., J Immunol 1999
  Evidence: mutant phenotype, assay, physical interaction, other species
• NCI Pathway Database IL2-mediated signaling events: IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GRB2/SOS1/GAB2/SHP2/PI3K complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SHC1-GRB2-SOS1-GAB2-PTPN11-PIK3CA-PIK3R1) → IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GRB2/SOS1/GAB2/SHP2 complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SHC1-GRB2-SOS1-GAB2-PTPN11) (modification, collaborate)
  Gadina et al., J Biol Chem 2000, Gu et al., Mol Cell Biol 2000, Merida et al., J Immunol 1991, Truitt et al., J Biol Chem 1994, Kanazawa et al., Cell Immunol 1994, Gómez et al., J Immunol 1997, Gadina et al., J Immunol 1999
  Evidence: mutant phenotype, assay, physical interaction, other species
• NCI Pathway Database IL2-mediated signaling events: PI3K complex (PIK3CA-PIK3R1) → IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GRB2/SOS1/GAB2/SHP2 complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SHC1-GRB2-SOS1-GAB2-PTPN11) (modification, collaborate)
  Gadina et al., J Biol Chem 2000, Gu et al., Mol Cell Biol 2000, Merida et al., J Immunol 1991, Truitt et al., J Biol Chem 1994, Kanazawa et al., Cell Immunol 1994, Gómez et al., J Immunol 1997, Gadina et al., J Immunol 1999
  Evidence: mutant phenotype, assay, physical interaction, other species
• NCI Pathway Database IL2 signaling events mediated by STAT5: IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GRB2/SOS1/GAB2/SHP2/PI3K complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SHC1-GRB2-SOS1-GAB2-PTPN11-PIK3CA-PIK3R1) → STAT5 (dimer)-active (STAT5B/STAT5A) (transcription, activates)
  Moriggl et al., Immunity 1999, Brennan et al., Immunity 1997
  Evidence: mutant phenotype, other species
• NCI Pathway Database IL3-mediated signaling events: IL3/IL3RA/CSF2RB (dodecamer)/JAK2/JAK2/SHC/GRB2/GAB2 complex (CSF2RB-JAK2-SHC1-GRB2-GAB2-IL3-IL3RA) → PI3K complex (PIK3CA-PIK3R1) (modification, collaborate)
  Gu et al., Mol Cell Biol 2000, Gu et al., Mol Cell 1998
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database IL3-mediated signaling events: IL3/IL3RA/CSF2RB (dodecamer)/JAK2/JAK2/SHC/GRB2/GAB2 complex (CSF2RB-JAK2-SHC1-GRB2-GAB2-IL3-IL3RA) → IL3/IL3RA/CSF2RB (dodecamer)/JAK2/JAK2/SHC/GRB2/GAB2/PI3K complex (CSF2RB-JAK2-SHC1-GRB2-GAB2-IL3-IL3RA-PIK3CA-PIK3R1) (modification, collaborate)
  Gu et al., Mol Cell Biol 2000, Gu et al., Mol Cell 1998
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database IL3-mediated signaling events: PI3K complex (PIK3CA-PIK3R1) → IL3/IL3RA/CSF2RB (dodecamer)/JAK2/JAK2/SHC/GRB2/GAB2/PI3K complex (CSF2RB-JAK2-SHC1-GRB2-GAB2-IL3-IL3RA-PIK3CA-PIK3R1) (modification, collaborate)
  Gu et al., Mol Cell Biol 2000, Gu et al., Mol Cell 1998
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database IL2-mediated signaling events: RAF1 (RAF1) → IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GRB2/SOS1/GAB2/SHP2/PI3K complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SHC1-GRB2-SOS1-GAB2-PTPN11-PIK3CA-PIK3R1) (modification, activates)
  Blanchard et al., Oncogene 2000, Lundin Brockdorff et al., Cytokine 2002, Karnitz et al., Mol Cell Biol 1995
  Evidence: mutant phenotype, other species
• NCI Pathway Database SHP2 signaling: RAF1 (RAF1) → IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GRB2/SOS1/GAB2/SHP2/PI3K complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SHC1-GRB2-SOS1-GAB2-PTPN11-PIK3CA-PIK3R1) (modification, activates)
  Blanchard et al., Oncogene 2000, Lundin Brockdorff et al., Cytokine 2002, Karnitz et al., Mol Cell Biol 1995
  Evidence: mutant phenotype
• NCI Pathway Database IL6-mediated signaling events: GRB2/SOS1/GAB family/SHP2 complex (GRB2-SOS1-GAB1_GAB2-PTPN11) → PI3K complex (PIK3CA-PIK3R1) (modification, collaborate)
  Takahashi-Tezuka et al., Mol Cell Biol 1998
  Evidence: mutant phenotype, physical interaction
• NCI Pathway Database IL6-mediated signaling events: GRB2/SOS1/GAB family/SHP2 complex (GRB2-SOS1-GAB1_GAB2-PTPN11) → GRB2/SOS1/GAB family/SHP2/PI3K complex (GRB2-SOS1-GAB1_GAB2-PTPN11-PIK3CA-PIK3R1) (modification, collaborate)
  Takahashi-Tezuka et al., Mol Cell Biol 1998
  Evidence: mutant phenotype, physical interaction
• NCI Pathway Database IL6-mediated signaling events: PI3K complex (PIK3CA-PIK3R1) → GRB2/SOS1/GAB family/SHP2/PI3K complex (GRB2-SOS1-GAB1_GAB2-PTPN11-PIK3CA-PIK3R1) (modification, collaborate)
  Takahashi-Tezuka et al., Mol Cell Biol 1998
  Evidence: mutant phenotype, physical interaction
• Reactome Reaction: GRB2 → PIK3CA (reaction) Nishida et al., Blood 1999, Wickrema et al., J Biol Chem 1999, Rodrigues et al., Mol Cell Biol 2000, Ong et al., Proc Natl Acad Sci U S A 2001, Guasch et al., Mol Cell Biol 2001, Demiroglu et al., Blood 2001, Agazie et al., Oncogene 2003, Jackson et al., Cancer Res 2004, Sordella et al., Science 2004, Chen et al., Proc Natl Acad Sci U S A 2004, Eswarakumar et al., Cytokine Growth Factor Rev 2005, Yu et al., J Immunol 2006, Takeda et al., Clin Cancer Res 2007, Sun et al., J Biol Chem 2008, Byron et al., Cancer Res 2008, Jackson et al., Hum Pathol 2010, Nishida et al., J Immunol 2011, Wesche et al., Biochem J 2011, Odai et al., J Biol Chem 1995, Anderson et al., J Biol Chem 1997, Hunter et al., Mol Endocrinol 1997, Feshchenko et al., J Biol Chem 1998, Park et al., J Immunol 1998, Gu et al., Mol Cell 1998
• Reactome Reaction: GRB2 → PIK3CA (indirect_complex) Nishida et al., Blood 1999, Rodrigues et al., Mol Cell Biol 2000, Ong et al., Proc Natl Acad Sci U S A 2001, Guasch et al., Mol Cell Biol 2001, Demiroglu et al., Blood 2001, Agazie et al., Oncogene 2003, Jackson et al., Cancer Res 2004, Sordella et al., Science 2004, Chen et al., Proc Natl Acad Sci U S A 2004, Eswarakumar et al., Cytokine Growth Factor Rev 2005, Yu et al., J Immunol 2006, Takeda et al., Clin Cancer Res 2007, Dufour et al., Bone 2008, Sun et al., J Biol Chem 2008, Byron et al., Cancer Res 2008, Jackson et al., Hum Pathol 2010, Nishida et al., J Immunol 2011, Wesche et al., Biochem J 2011, Odai et al., J Biol Chem 1995, Anderson et al., J Biol Chem 1997, Hunter et al., Mol Endocrinol 1997, Feshchenko et al., J Biol Chem 1998, Park et al., J Immunol 1998

Protein-Protein interactions - manually collected from original source literature:

Studies that report less than 10 interactions are marked with *

• IRef Biogrid Interaction: PIK3CA — GRB2 (physical association, affinity chromatography technology) Brehme et al., Proc Natl Acad Sci U S A 2009
• IRef Biogrid Interaction: PIK3CA — GRB2 (physical association, affinity chromatography technology) Bisson et al., Nat Biotechnol 2011
• IRef Intact Interaction: Complex of 29 proteins (association, tandem affinity purification) Li et al., Molecular systems biology 2013
• IRef Intact Interaction: Complex of 40 proteins (association, tandem affinity purification) Li et al., Molecular systems biology 2013
• IRef Intact Interaction: Complex of 13 proteins (association, tandem affinity purification) Brehme et al., Proc Natl Acad Sci U S A 2009
• IRef Intact Interaction: Complex of 12 proteins (association, tandem affinity purification) Brehme et al., Proc Natl Acad Sci U S A 2009

Text-mined interactions from Literome

Wheeler et al., Mol Cell Biol 2001 : Interaction with Grb2 dramatically increased the catalytic activity of this PI3K
Choi et al., J Recept Signal Transduct Res 2004 : PI3K inhibition increased IRS-1-Grb2 complex formation and ras activity following insulin treatment of cells
Radhakrishnan et al., J Biol Chem 2008 (MAP Kinase Signaling System) : Cellular exposure to 25 mm glucose, which is required for Shc phosphorylation in response to IGF-I, resulted in enhanced Grb2 binding to p85, activation of PI3K activity, and increased AKT phosphorylation as compared with cells exposed to 5 mm glucose
Kim et al., Endocrinology 1998 (Neuroblastoma) : However, even though the PI 3-K inhibitors enhanced the association of Grb2 with IRS-2, these compounds suppressed IGF-I induced mitogen activated protein kinase activation and neurite outgrowth