◀ Back to IRS1
IGF1R — IRS1
Pathways - manually collected, often from reviews:
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OpenBEL Selventa BEL large corpus:
O/5 complex ()
→
Complex of IGF1R-IRS1
(increases, IGF1R/IRS1 Activity)
Evidence: Ligand binding to the extracellular subunits leads to activation of the intrinsic tyrosine kinases of the transmembrane subunits. The ATP-binding site at Lys1003 and the tyrosine kinase domain are required for all functions of the IGF-IR. Trans-phosphorylation between the subunits involves Tyr1131, 1135 and 1136 in the kinase domain and leads to full activation of kinase activity. Other tyrosine phosphorylated sites serve to recruit specific adaptor molecules via their SH2-binding domains. Phosp...
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OpenBEL Selventa BEL large corpus:
IRS1
→
IGF1R
(directlyIncreases, IRS1 Activity)
Evidence: upon binding of IGF1, the IGFR, which is a receptor tyrosine kinase, becomes phosphorylated and recruits the substrate IRS1, leading to the activation of the lipid kinase PI3K
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OpenBEL Selventa BEL large corpus:
IRS1
→
IGF1R
(directlyIncreases, IRS1 Activity)
Evidence: from http://www.ub.rug.nl/eldoc/dis/medicine/n.wilczak/c1.pdf The intrinsic tyrosine kinase activity of the IGF-I receptor is enhanced and phosphorylates multiple substrates, including IRS1 and IRS2 on tyrosine residues
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OpenBEL Selventa BEL large corpus:
IRS1
→
IGF1R
(directlyIncreases, IRS1 Activity)
Ishikawa et al., J Clin Exp Hematop 2006*
Evidence: Accordingly, under the cellular context of the elevated expression of IL- 6Ra on myeloma cells, it is assumed that IL-6Ra molecules are located close to IGF-I receptors at lipid rafts, and IL-6 stimulation triggers the complex formation of IL-6Ra not only with gp130 but also with IGF-I receptors, leading to autophosphorylation of IGF-I receptor b and subsequent acti- vation of PI-3 kinase-Akt pathways (Fig. 4) 79 .
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OpenBEL Selventa BEL large corpus:
IRS1
→
IGF1R
(directlyIncreases, IRS1 Activity)
Evidence: At least nine intracellular substrates of the insulin/IGF-I receptor kinases have been identified (Fig. 2). Four of these belong to the family of insulin-receptor substrate (IRS) proteins9. Other substrates include Gab-1, p60dok, Cbl, APS and isoforms of Shc10.
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OpenBEL Selventa BEL large corpus:
IRS1
→
IGF1R
(increases, IGF1R Activity)
Hernández-Sánchez et al., J Biol Chem 1995*
Evidence: We have studied the effect of double tyrosine mutations on IGF-I induced receptor autophosphorylation, activation of Shc and IRS-1 pathways, and cell proliferation and tumorigenicity. Substitution of tyrosines 1131/1135 blocks any detectable autophosphorylation, whereas substitution of tyrosines 1131/1136 or 1135/1136 only reduces autophosphorylation levels in some clones by approximately 50%. Nevertheless, all the cells expressing IGF-I receptors with double tyrosine substitutions demonstrated ...
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BioCarta igf-1 signaling pathway:
IGF-1 (IGF1)
→
IGF-1R-alpha/IGF-1R-alpha/IGF-1R-beta/IGF-1R-beta/IRS-1 complex (IRS1-IGF1R)
(modification, collaborate)
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BioCarta igf-1 signaling pathway:
IGF-1/IGF-1/IGF-1R-alpha/IGF-1R-alpha/IGF-1R-beta/IGF-1R-beta complex (IGF1-IGF1R)
→
IRS-1 (IRS1)
(modification, collaborate)
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BioCarta igf-1 signaling pathway:
IGF-1/IGF-1/IGF-1R-alpha/IGF-1R-alpha/IGF-1R-beta/IGF-1R-beta complex (IGF1-IGF1R)
→
IGF-1R-alpha/IGF-1R-alpha/IGF-1R-beta/IGF-1R-beta/IRS-1 complex (IRS1-IGF1R)
(modification, collaborate)
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BioCarta igf-1 signaling pathway:
IRS-1 (IRS1)
→
IGF-1R-alpha/IGF-1R-alpha/IGF-1R-beta/IGF-1R-beta/IRS-1 complex (IRS1-IGF1R)
(modification, collaborate)
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BioCarta the igf-1 receptor and longevity:
IGF-1 (IGF1)
→
IGF-1R-alpha/IGF-1R-alpha/IGF-1R-beta/IGF-1R-beta/IRS-1 complex (IRS1-IGF1R)
(modification, collaborate)
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BioCarta the igf-1 receptor and longevity:
IGF-1/IGF-1/IGF-1R-alpha/IGF-1R-alpha/IGF-1R-beta/IGF-1R-beta complex (IGF1-IGF1R)
→
IRS-1 (IRS1)
(modification, collaborate)
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BioCarta the igf-1 receptor and longevity:
IGF-1/IGF-1/IGF-1R-alpha/IGF-1R-alpha/IGF-1R-beta/IGF-1R-beta complex (IGF1-IGF1R)
→
IGF-1R-alpha/IGF-1R-alpha/IGF-1R-beta/IGF-1R-beta/IRS-1 complex (IRS1-IGF1R)
(modification, collaborate)
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BioCarta the igf-1 receptor and longevity:
IRS-1 (IRS1)
→
IGF-1R-alpha/IGF-1R-alpha/IGF-1R-beta/IGF-1R-beta/IRS-1 complex (IRS1-IGF1R)
(modification, collaborate)
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NCI Pathway Database Integrins in angiogenesis:
IGF-1R heterotetramer/IGF1/IRS1/Shp2 complex (IGF1R-IGF1-IRS1-PTPN11)
→
SHP2 (PTPN11)
(modification, collaborate)
Kuemmerle et al., Am J Physiol Gastrointest Liver Physiol 2006
Evidence: assay, physical interaction
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NCI Pathway Database Integrins in angiogenesis:
IGF-1R heterotetramer/IGF1/IRS1/Shp2 complex (IGF1R-IGF1-IRS1-PTPN11)
→
IGF-1R heterotetramer/IGF1/IRS1 complex (IGF1R-IGF1-IRS1)
(modification, collaborate)
Kuemmerle et al., Am J Physiol Gastrointest Liver Physiol 2006
Evidence: assay, physical interaction
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NCI Pathway Database Integrins in angiogenesis:
SHP2 (PTPN11)
→
IGF-1R heterotetramer/IGF1/IRS1 complex (IGF1R-IGF1-IRS1)
(modification, collaborate)
Kuemmerle et al., Am J Physiol Gastrointest Liver Physiol 2006
Evidence: assay, physical interaction
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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
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NCI Pathway Database IGF1 pathway:
IGF-1R heterotetramer/IGF1/IRS1/Shp2 complex (IGF1R-IGF1-IRS1-PTPN11)
→
SHP2 (PTPN11)
(modification, collaborate)
Amoui et al., J Endocrinol 2001*
Evidence: assay, physical interaction
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NCI Pathway Database IGF1 pathway:
IGF-1R heterotetramer/IGF1/IRS1/Shp2 complex (IGF1R-IGF1-IRS1-PTPN11)
→
IGF-1R heterotetramer/IGF1/IRS1 complex (IGF1R-IGF1-IRS1)
(modification, collaborate)
Amoui et al., J Endocrinol 2001*
Evidence: assay, physical interaction
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NCI Pathway Database IGF1 pathway:
SHP2 (PTPN11)
→
IGF-1R heterotetramer/IGF1/IRS1 complex (IGF1R-IGF1-IRS1)
(modification, collaborate)
Amoui et al., J Endocrinol 2001*
Evidence: assay, physical interaction
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NCI Pathway Database Integrins in angiogenesis:
Erk1-2 (MAPK3/MAPK1)
→
IGF-1R heterotetramer/IGF1/IRS1 complex (IGF1R-IGF1-IRS1)
(modification, collaborate)
Kuemmerle et al., Am J Physiol Gastrointest Liver Physiol 2006
Evidence: assay
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NCI Pathway Database IGF1 pathway:
IGF-1R heterotetramer/IGF1/IRS1 complex (IGF1R-IGF1-IRS1)
→
GRB2/SOS1 complex (GRB2-SOS1)
(modification, collaborate)
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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)
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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)
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NCI Pathway Database Integrins in angiogenesis:
IRS1 (IRS1)
→
IGF-1R heterotetramer complex (IGF1R)
(modification, collaborate)
Kuemmerle et al., Am J Physiol Gastrointest Liver Physiol 2006
Evidence: assay, physical interaction
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NCI Pathway Database Integrins in angiogenesis:
IRS1 (IRS1)
→
IGF-1R heterotetramer/IGF1/IRS1 complex (IGF1R-IGF1-IRS1)
(modification, collaborate)
Kuemmerle et al., Am J Physiol Gastrointest Liver Physiol 2006
Evidence: assay, physical interaction
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NCI Pathway Database Integrins in angiogenesis:
IGF-1R heterotetramer complex (IGF1R)
→
IGF-1R heterotetramer/IGF1/IRS1 complex (IGF1R-IGF1-IRS1)
(modification, collaborate)
Kuemmerle et al., Am J Physiol Gastrointest Liver Physiol 2006
Evidence: assay, physical interaction
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NCI Pathway Database Integrins in angiogenesis:
Fibronectin (FN1)
→
IGF-1R heterotetramer/IGF1/IRS1 complex (IGF1R-IGF1-IRS1)
(modification, activates)
Kuemmerle et al., Am J Physiol Gastrointest Liver Physiol 2006
Evidence: assay, physical interaction
-
NCI Pathway Database Integrins in angiogenesis:
IGF1 (IGF1)
→
IGF-1R heterotetramer/IGF1/IRS1 complex (IGF1R-IGF1-IRS1)
(modification, collaborate)
Kuemmerle et al., Am J Physiol Gastrointest Liver Physiol 2006
Evidence: assay, physical interaction
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NCI Pathway Database IGF1 pathway:
IRS2/Crk complex (IRS2-CRK)
→
IGF-1R heterotetramer/IGF1/IRS1 complex (IGF1R-IGF1-IRS1)
(modification, collaborate)
Beitner-Johnson et al., J Biol Chem 1996
Evidence: mutant phenotype, assay
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NCI Pathway Database Integrins in angiogenesis:
IGF-1R heterotetramer/IGF1/IRS1 complex (IGF1R-IGF1-IRS1)
→
p70S6K (RPS6KB1)
(modification, activates)
Kuemmerle et al., Am J Physiol Gastrointest Liver Physiol 2006
Evidence: assay
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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
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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
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NCI Pathway Database IGF1 pathway:
IGF-1R heterotetramer/IGF1/IRS1 complex (IGF1R-IGF1-IRS1)
→
PI3K complex (PIK3CA-PIK3R1)
(modification, activates)
Mur et al., Endocrinology 2003
Evidence: assay
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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
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NCI Pathway Database IGF1 pathway:
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos complex (IGF1R-IGF1-IRS1-GRB2-SOS1)
→
HRAS/GDP complex (HRAS)
(modification, activates)
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NCI Pathway Database IGF1 pathway:
IGF-1R heterotetramer/IGF1/IRS1 complex (IGF1R-IGF1-IRS1)
→
Paxillin (PXN)
(modification, activates)
Butler et al., J Biol Chem 1997, Fagerström et al., J Biol Chem 1998, Casamassima et al., J Biol Chem 1998
Evidence: assay, physical interaction
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NCI Pathway Database IGF1 pathway:
IGF-1R heterotetramer/IGF1/IRS1 complex (IGF1R-IGF1-IRS1)
→
CRK (CRK)
(modification, activates)
Butler et al., J Biol Chem 1997, Fagerström et al., J Biol Chem 1998, Casamassima et al., J Biol Chem 1998
Evidence: assay, physical interaction
-
NCI Pathway Database IGF1 pathway:
IGF-1R heterotetramer/IGF1/IRS1 complex (IGF1R-IGF1-IRS1)
→
p130 Cas (BCAR1)
(modification, activates)
Butler et al., J Biol Chem 1997, Fagerström et al., J Biol Chem 1998, Casamassima et al., J Biol Chem 1998
Evidence: assay, physical interaction
-
NCI Pathway Database IGF1 pathway:
IGF-1R heterotetramer/IGF1/IRS1 complex (IGF1R-IGF1-IRS1)
→
Crk/p130 Cas/Paxillin complex (CRK-BCAR1-PXN)
(modification, activates)
Butler et al., J Biol Chem 1997, Fagerström et al., J Biol Chem 1998, Casamassima et al., J Biol Chem 1998
Evidence: assay, physical interaction
-
NCI Pathway Database IGF1 pathway:
IGF-1R heterotetramer/IGF1/IRS1 complex (IGF1R-IGF1-IRS1)
→
IGF-1R heterotetramer/IGF1 complex (IGF1R-IGF1)
(translocation, collaborate)
Panetta et al., Biochem Biophys Res Commun 2004*
Evidence: mutant phenotype, assay, physical interaction
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NCI Pathway Database IGF1 pathway:
IGF-1R heterotetramer/IGF1/IRS1 complex (IGF1R-IGF1-IRS1)
→
IRS1 (IRS1)
(translocation, collaborate)
Panetta et al., Biochem Biophys Res Commun 2004*
Evidence: mutant phenotype, assay, physical interaction
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NCI Pathway Database IGF1 pathway:
IGF-1R heterotetramer/IGF1 complex (IGF1R-IGF1)
→
IRS1 (IRS1)
(translocation, collaborate)
Panetta et al., Biochem Biophys Res Commun 2004*
Evidence: mutant phenotype, assay, physical interaction
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NCI Pathway Database IGF1 pathway:
IGF-1R heterotetramer/IGF1 complex (IGF1R-IGF1)
→
IRS1/NCK2 complex (NCK2-IRS1)
(modification, collaborate)
Lee et al., Proc Natl Acad Sci U S A 1993
Evidence: physical interaction
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NCI Pathway Database IGF1 pathway:
IGF-1R heterotetramer/IGF1 complex (IGF1R-IGF1)
→
IGF-1R heterotetramer/IGF1/IRS/Nck complex (IGF1R-IGF1-NCK2-IRS1)
(modification, collaborate)
Lee et al., Proc Natl Acad Sci U S A 1993
Evidence: physical interaction
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NCI Pathway Database IGF1 pathway:
IRS1/NCK2 complex (NCK2-IRS1)
→
IGF-1R heterotetramer/IGF1/IRS/Nck complex (IGF1R-IGF1-NCK2-IRS1)
(modification, collaborate)
Lee et al., Proc Natl Acad Sci U S A 1993
Evidence: physical interaction
-
NCI Pathway Database IGF1 pathway:
IGF-1R heterotetramer/IGF1/IRS1 complex (IGF1R-IGF1-IRS1)
→
IRS1/Crk complex (IRS1-CRK)
(modification, activates)
Beitner-Johnson et al., J Biol Chem 1995*, Beitner-Johnson et al., J Biol Chem 1996, Koval et al., Biochem J 1998
Evidence: mutant phenotype, assay
-
Reactome Reaction:
IGF1R
→
IRS1
(indirect_complex)
Qu et al., J Biol Chem 1999*, Karas et al., Endocrinology 2001, Huang et al., FEBS Lett 2001*, Schreyer et al., Endocrinology 2003, Kim et al., Oncogene 2004, Karlsson et al., Eur J Biochem 2004*, Rakatzi et al., Arch Physiol Biochem 2006, Cuevas et al., J Hepatol 2007, Craparo et al., J Biol Chem 1995*, He et al., J Biol Chem 1995*, Siemeister et al., J Biol Chem 1995, Xu et al., J Biol Chem 1995, Takahashi et al., Endocrinology 1997, Fantin et al., J Biol Chem 1998, Kim et al., Endocrinology 1998, Kim et al., J Biol Chem 1998
-
Reactome Reaction:
IGF1R
→
IRS1
(reaction)
Qu et al., J Biol Chem 1999*, Karas et al., Endocrinology 2001, Huang et al., FEBS Lett 2001*, Schreyer et al., Endocrinology 2003, Kim et al., Oncogene 2004, Karlsson et al., Eur J Biochem 2004*, Rakatzi et al., Arch Physiol Biochem 2006, Cuevas et al., J Hepatol 2007, Craparo et al., J Biol Chem 1995*, He et al., J Biol Chem 1995*, Siemeister et al., J Biol Chem 1995, Xu et al., J Biol Chem 1995, Takahashi et al., Endocrinology 1997, Fantin et al., J Biol Chem 1998, Kim et al., Endocrinology 1998, Kim et al., J Biol Chem 1998
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WikiPathways Factors and pathways affecting insulin-like growth factor (IGF1)-Akt signaling:
IGF1R
→
IRS1
(activation)
-
WikiPathways Focal Adhesion-PI3K-Akt-mTOR-signaling pathway:
FGFR2/KDR/INSR/FGFR3/IGF1R/KIT/FGFR1/EPHA2/EGFR/CSF1R/FGFR4/FLT1/FLT4/NGFR/MET/PDGFRA/PDGFRB/TEK
→
IRS1/IRS4/IRS2
(activation)
-
WikiPathways Insulin Signaling:
IGF1R
→
SHC3/IRS1/IRS2/SHC1/IRS4/SHC2/GAB1
(activation)
-
WikiPathways Signaling Pathways in Glioblastoma:
IGF1R/ERBB3/FGFR1/PDGFRA/PDGFRB/ERBB2/EGFR/FGFR2/MET
→
IRS1
(mim-stimulation)
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
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IRef Bind Interaction:
IGF1R
—
IRS1
Arbet-Engels et al., J Biol Chem 1999*
-
IRef Bind Interaction:
IGF1R
—
IRS1
Craparo et al., J Biol Chem 1995*
-
IRef Bind_translation Interaction:
IGF1R
—
IRS1
(two hybrid)
Craparo et al., J Biol Chem 1995*
-
IRef Bind_translation Interaction:
IGF1R
—
IRS1
(two hybrid)
Arbet-Engels et al., J Biol Chem 1999*
-
IRef Biogrid Interaction:
IGF1R
—
IRS1
(direct interaction, two hybrid)
Tartare-Deckert et al., J Biol Chem 1995*
-
IRef Biogrid Interaction:
IGF1R
—
IRS1
(direct interaction, two hybrid)
Dey et al., Mol Endocrinol 1996
-
IRef Biogrid Interaction:
IGF1R
—
IRS1
(physical association, affinity chromatography technology)
Mañes et al., Mol Cell Biol 1999*
-
IRef Hprd Interaction:
IGF1R
—
IRS1
(in vivo)
Hers et al., Biochem J 2002*, Klammt et al., Biochem Biophys Res Commun 2005*, Tartare-Deckert et al., J Biol Chem 1995*, Xu et al., J Biol Chem 1995, He et al., J Biol Chem 1996*
-
IRef Hprd Interaction:
IGF1R
—
IRS1
(two hybrid)
Hers et al., Biochem J 2002*, Klammt et al., Biochem Biophys Res Commun 2005*, Tartare-Deckert et al., J Biol Chem 1995*, Xu et al., J Biol Chem 1995, He et al., J Biol Chem 1996*
-
IRef Intact Interaction:
IGF1R
—
IRS1
(physical association, two hybrid)
Craparo et al., J Biol Chem 1995*
-
IRef Ophid Interaction:
IGF1R
—
IRS1
(aggregation, interologs mapping)
Brown et al., Bioinformatics 2005
Text-mined interactions from Literome
Boney et al., Mol Endocrinol 2000
:
IGF-I induces signaling pathways that involve
IGF-I receptor mediated tyrosine phosphorylation of Shc and
insulin receptor substrate 1 (IRS-1)
Allard et al., American journal of physiology. Renal physiology 2007
(Albuminuria...) :
The early phase of diabetes was found to be associated with an increase in glomerular expression of
IGF1-R , PDGF-R, and TGF-beta-RII and
activation of
IRS1 , Erk 1/2, and Smad 2/3
Leclerc et al., Journal of molecular signaling 2010
:
Inhibition of
IGF-1R signaling using the tyrosine kinase inhibitor HNMPA ( AM ) 3
resulted in significant decrease in
P-IRS-1 ( Ser794 ) and P-Akt ( Thr308 )
Xuan et al., J Biol Chem 2010
(Diabetes Mellitus...) :
To examine genetically the
involvement of
Irs1 and Irs2 in
Igf1r signaling, we generated double mutant mice lacking Igf1r specifically in pancreatic ß cells in an Irs1- or Irs2-null background
Sun et al., Endocrinology 2011
:
No alterations were observed in downstream signaling targets of prolactin and progesterone, suggesting that activation of the
IGF-1R may directly
regulate expression of
IRS-1/2 during alveolar development and differentiation
Xie et al., Cancer cell international 2013
:
Klotho is a tumor suppressor in gastric cancer, which regulates
IGF-1R phosphorylation and the subsequent
activation of
IRS-1/PI3K/Akt/mTOR signaling, tumor cell proliferation, apoptosis, and autophagy
Myers et al., Endocrinology 1993
:
The insulin-like growth factor-I
(IGF-I) receptor also
mediated the tyrosine phosphorylation of
IRS-1 and increased the amount of PtdIns 3'-kinase activity bound to IRS-1 in Chinese hamster ovary cells
Takahashi et al., Endocrinology 1997
:
Roles of
insulin receptor substrate-1 and Shc on
insulin-like growth factor I receptor signaling in early passages of cultured human fibroblasts