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GRB2 — IRS1

Pathways - manually collected, often from reviews:

• OpenBEL Selventa BEL large corpus: Complex of GRB2-IRS1 → PTEN (decreases, GRB2/IRS1 Activity) Weng et al., Hum Mol Genet 2001*
  Evidence: The latter was accompanied by a decrease in the phosphorylation of insulin receptor substrate 1 (IRS-1) and the association of IRS-1 with Grb2/Sos
• BioCarta insulin signaling pathway: IRS-1 (IRS1) → GRB2 (modification, activates)
• BioCarta igf-1 signaling pathway: IRS-1 (IRS1) → GRB2 (modification, activates)
• KEGG Insulin signaling pathway: IRS1/IRS2/IRS4 → GRB2 (protein-protein, activation)
• NCI Pathway Database IGF1 pathway: IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1 complex (IGF1R-IGF1-IRS1-GNB2L1-GRB2-SHC1-SOS1) → PKC mu (PRKD1) (modification, activates) Hermanto et al., Mol Cell Biol 2002
  Evidence: assay, physical interaction
• 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: 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 IGF1 pathway: IGF-1R heterotetramer/IGF1/IRS1 complex (IGF1R-IGF1-IRS1) → GRB2/SOS1 complex (GRB2-SOS1) (modification, collaborate)
  
• NCI Pathway Database IGF1 pathway: IGF-1R heterotetramer/IGF1/IRS1 complex (IGF1R-IGF1-IRS1) → IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos complex (IGF1R-IGF1-IRS1-GRB2-SOS1) (modification, collaborate)
  
• NCI Pathway Database IGF1 pathway: GRB2/SOS1 complex (GRB2-SOS1) → IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos complex (IGF1R-IGF1-IRS1-GRB2-SOS1) (modification, collaborate)
  
• 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: IRS1 (IRS1) → GRB2 (GRB2) (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/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/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/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/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: 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 IGF1 pathway: IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc complex (IGF1R-IGF1-GRB2-SHC1-SOS1) → IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1 complex (IGF1R-IGF1-IRS1-GNB2L1-GRB2-SHC1-SOS1) (modification, collaborate)
  Hermanto et al., Mol Cell Biol 2002, Kiely et al., J Biol Chem 2005
  Evidence: assay, physical interaction
• NCI Pathway Database IGF1 pathway: IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1 complex (IGF1R-IGF1-IRS1-GNB2L1-GRB2-SHC1-SOS1) → RACK1 (GNB2L1) (modification, collaborate) Hermanto et al., Mol Cell Biol 2002, Kiely et al., J Biol Chem 2005
  Evidence: 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 IGF1 pathway: IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1 complex (IGF1R-IGF1-IRS1-GNB2L1-GRB2-SHC1-SOS1) → PKC delta (PRKCD) (modification, activates) Hermanto et al., Mol Cell Biol 2002
  Evidence: assay, physical interaction
• NCI Pathway Database Signaling events mediated by PTP1B: PTP1B (PTPN1) → PTP1B/IRS1/GRB2 complex (PTPN1-IRS1-GRB2) (modification, collaborate)
  Goldstein et al., J Biol Chem 2000
  Evidence: assay, other species
• NCI Pathway Database Signaling events mediated by PTP1B: GRB2 (GRB2) → IRS1 (IRS1) (modification, collaborate) Goldstein et al., J Biol Chem 2000
  Evidence: assay, other species
• NCI Pathway Database Signaling events mediated by PTP1B: GRB2 (GRB2) → PTP1B/IRS1/GRB2 complex (PTPN1-IRS1-GRB2) (modification, collaborate)
  Goldstein et al., J Biol Chem 2000
  Evidence: assay, other species
• NCI Pathway Database Signaling events mediated by PTP1B: IRS1 (IRS1) → PTP1B/IRS1/GRB2 complex (PTPN1-IRS1-GRB2) (modification, collaborate)
  Goldstein et al., J Biol Chem 2000
  Evidence: assay, other species
• NCI Pathway Database IGF1 pathway: IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos complex (IGF1R-IGF1-IRS1-GRB2-SOS1) → HRAS/GDP complex (HRAS) (modification, activates)
• 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 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
• Reactome Reaction: GRB2 → IRS1 (indirect_complex) Skolnik et al., Science 1993, Xu et al., J Biol Chem 1995, Ward et al., J Biol Chem 1996*, Okada et al., J Biol Chem 1996, Takahashi et al., Endocrinology 1997, Kim et al., Endocrinology 1998, Kim et al., J Biol Chem 1998
• Reactome Reaction: GRB2 → IRS1 (direct_complex)
• Reactome Reaction: GRB2 → IRS1 (reaction) Skolnik et al., Science 1993, Xu et al., J Biol Chem 1995, Ward et al., J Biol Chem 1996*, Okada et al., J Biol Chem 1996, Takahashi et al., Endocrinology 1997, Kim et al., Endocrinology 1998, Kim et al., J Biol Chem 1998
• WikiPathways EPO Receptor Signaling: Complex of GRB2-RAF1-SOS1-IRS2-JAK2-IRS1-RASA1 → MAP2K1 (activation)
• WikiPathways Insulin Signaling: SHC3/IRS1/IRS2/SHC1/IRS4/SHC2/GAB1 → RAC1/GRB2/SOS1/RAC2/RRAD/GRB14/SOS2/RAF1/HRAS/GRB10 (activation)
  

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

Studies that report less than 10 interactions are marked with *

• IRef Biogrid Interaction: IRS1 — GRB2 (direct interaction, unspecified method) Liu et al., Cell communication and signaling : CCS 2012
• IRef Biogrid Interaction: IRS1 — GRB2 (physical association, affinity chromatography technology) Bisson et al., Nat Biotechnol 2011
• IRef Biogrid Interaction: IRS1 — GRB2 (physical association, affinity chromatography technology) Skolnik et al., EMBO J 1993
• IRef Biogrid Interaction: IRS1 — GRB2 (direct interaction, pull down) Skolnik et al., EMBO J 1993
• IRef Biogrid Interaction: IRS1 — GRB2 (physical association, affinity chromatography technology) Morrison et al., Oncogene 2002*
• IRef Biogrid Interaction: IRS1 — GRB2 (direct interaction, pull down) Giorgetti-Peraldi et al., Eur J Biochem 1995*
• IRef Dip Interaction: GRB2 — IRS1 (physical association, biophysical) Myers et al., Ann N Y Acad Sci 1995*
• IRef Dip Interaction: GRB2 — IRS1 (physical association, genetic interference) Skolnik et al., EMBO J 1993
• IRef Hprd Interaction: IRS1 — GRB2 (in vitro) Wang et al., Biochem Biophys Res Commun 1995*, Tobe et al., J Biol Chem 1993*, Okada et al., J Biol Chem 1996
• IRef Hprd Interaction: IRS1 — GRB2 (in vivo) Wang et al., Biochem Biophys Res Commun 1995*, Tobe et al., J Biol Chem 1993*, Okada et al., J Biol Chem 1996
• IRef Ophid Interaction: GRB2 — IRS1 (aggregation, interologs mapping) Brown et al., Bioinformatics 2005

Text-mined interactions from Literome

Liu et al., Am J Physiol Endocrinol Metab 2009 (Insulin Resistance) : Suppressing Grb2 expression in C ( 2 ) C ( 12 ) myoblasts enhances insulin stimulated insulin receptor substrate (IRS)-1 , tyrosine phosphorylation, and Akt phosphorylation, which is associated with decreased IRS-1 serine phosphorylation at residues 307, 612, and 636/639
Chen et al., Mol Cell Biol 1995 : Although overexpression of IRS-1 increased IRS-1 binding to Grb-2 , ERK-1/ERK-2 activation was not rescued
Mèndez et al., Mol Cell Biol 1996 : Stimulation of general protein synthesis does not involve activation by IRS-1 of GRB-2-SOS-p21ras or SH-PTP2, since IRS-1 variants lacking the SH2 binding Tyr residues for these proteins are fully active