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GRB2 — INS
Pathways - manually collected, often from reviews:
-
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)
-
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
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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 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:
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:
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:
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:
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/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:
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)
→
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:
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
Text-mined interactions from Literome
Wada et al., Endocrinology 1999
:
Insulin stimulation of Shc association with
Grb2 , which is important for p21ras-MAP kinase activation, was decreased by overexpression of WT- and 2F-SHIP ... Importantly,
insulin induced Shc x
Grb2 association was not detectably reduced in deltaSH2-SHIP cells
Tsakiridis et al., Microsc Res Tech 1999
:
Intact actin filaments appear to be essential for mediation of early events such as association of Shc with
Grb2 in
response to
insulin , which leads to stimulation of gene expression
Uchida et al., Mol Cell Biol 2000
:
Insulin promoted the association of
Grb-2 with IRS-1 and IRS-4, whereas IRS-2 weakly bound Grb-2 ; consequently, IRS-1 and IRS-4 enhanced insulin stimulated mitogen activated protein kinase activity
Nakajima et al., J Biol Chem 2000
(Carcinoma, Hepatocellular) :
In contrast,
insulin induced association of Shc and
Grb2 was not inhibited
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
Valverde et al., Mol Cell Biol 2001
:
Association of insulin receptor substrate 1 (IRS-1) y895 with
Grb-2 mediates the
insulin signaling involved in IRS-1-deficient brown adipocyte mitogenesis ... Reconstitution of IRS-1-deficient brown adipocytes with wild-type IRS-1 restored
insulin induced IRS-1 and SHC tyrosine phosphorylation and
IRS-1-Grb-2 , IRS-1-SHC, and SHC-Grb-2 associations, leading to the activation of MAPK and enhancement of DNA synthesis
Mur et al., Diabetes 2002
:
However, SHC expression and SHC tyrosine phosphorylation and its association with
Grb-2 were unaltered in
response to
insulin in IGF-IR -- deficient brown adipocytes
Sano et al., J Biol Chem 2002
:
The results from the overexpression of IRAS, where its amount was about the same as that of IRS-4, indicated that IRAS associated directly with IRS-4 and showed that the increased complexation of IRS-4 with IRAS did not alter the
insulin stimulated tyrosine phosphorylation of IRS-4 or the association of IRS-4 with phosphatidylinositol 3-kinase or
Grb2
Lee et al., J Biol Chem 2003
:
Insulin stimulation of JNK activity
required phosphatidylinositol 3-kinase and
Grb2 signaling
Arribas et al., J Biol Chem 2003
:
However, although
insulin promoted the association of
Grb-2 with recombinant IRS-3 in IRS-1-/- cells, the exogenous expression of this IRS family member failed to activate p42/44 MAPK and mitogenesis in brown adipocytes lacking IRS-1
Biedi et al., Endocrinology 2003
:
Here we show that
insulin also
induces Shc phosphorylation and
Grb2 recruitment to caveolae, but with a significantly different time course compared with IGF-I
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
Cherniack et al., J Biol Chem 1995
:
Immunoblot analysis of these precipitates revealed that
insulin causes a marked hyperphosphorylation of Sos1 and a 50 % decrease in
Grb2 associated with Sos proteins under these conditions
Yamauchi et al., Mol Cell Biol 1994
:
Further, expression of Grb2 in parental CHO cells had no effect on insulin signaling, whereas
Grb2 increased
insulin activation of reporter gene expression in CHO/IR cells ... 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
Pronk et al., Mol Cell Biol 1994
:
From these results, we conclude that after insulin and EGF treatment, Shc associates with both
Grb2 and mSOS and therefore may
mediate , at least in part,
insulin- and EGF induced activation of p21ras
Myers et al., Mol Cell Biol 1994
:
Role of
IRS-1-GRB-2 complexes in
insulin signaling
Ohmichi et al., J Biol Chem 1994
:
NGF and EGF also
induced the association of Shc proteins with a Grb2 fusion protein or endogenous
Grb2 , whereas
insulin had no effect
Tobe et al., J Biol Chem 1993
:
Insulin stimulates association of insulin receptor substrate-1 with the protein abundant Src
homology/growth factor receptor bound protein 2
Skolnik et al., EMBO J 1993
:
In this report we show that in
response to
insulin ,
GRB2 forms a stable complex with two tyrosine phosphorylated proteins
Zhang-Sun et al., Endocrinology 1996
(Liver Neoplasms, Experimental) :
A 60-kilodalton protein in rat hepatoma cells overexpressing insulin receptor was tyrosine phosphorylated and associated with Syp, phophatidylinositol 3-kinase, and
Grb2 in an
insulin dependent manner ... Studies in rat liver, muscle, and adipose tissue identified
insulin dependent association of Syp,
Grb2 , and p85 with tyrosine phosphorylated p60 in adipose tissue only
Ishihara et al., J Biol Chem 1997
:
Insulin induced Shc phosphorylation and subsequent association with
Grb2 was enhanced in WT-Shc cells
Srinivas et al., Cell Signal 1996
:
alpha 2-HSG inhibits
insulin induced tyrosine phosphorylation of IRS-1 and the subsequent association of
GRB2 , as well as Sos, with IRS-1
Valverde et al., Mol Endocrinol 1998
:
Furthermore,
insulin/IGF-I stimulated IRS-1 associated
Grb-2 phosphorylation
Karoor et al., J Biol Chem 1998
:
The Tyr-350 -- > Phe mutant form of the beta2-adrenergic receptor, lacking the site for tyrosine phosphorylation, fails to bind
Grb2 in
response to
insulin , fails to display internalization of beta2-adrenergic receptor in response to insulin, and is no longer subject to the counter-regulatory effects of insulin on cyclic AMP accumulation