◀ Back to IGF1
IGF1 — SHC1
Pathways - manually collected, often from reviews:
-
BioCarta multiple antiapoptotic pathways from igf-1r signaling lead to bad phosphorylation:
IGF-1/IGF-1/IGF-1R-alpha/IGF-1R-alpha/IGF-1R-beta/IGF-1R-beta/14-3-3 complex (IGF1R-YWHAH-IGF1)
→
SHC/GRB2/SOS-1 complex (SOS1-GRB2-SHC1)
(modification, activates)
-
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)
→
SHC/GRB2/SOS-1 complex (SOS1-GRB2-SHC1)
(modification, activates)
-
BioCarta igf-1 signaling pathway:
IGF-1/IGF-1/IGF-1R-alpha/IGF-1R-alpha/IGF-1R-beta/IGF-1R-beta complex (IGF1-IGF1R)
→
SHC/GRB2/SOS-1 complex (SOS1-GRB2-SHC1)
(modification, activates)
-
BioCarta nfat and hypertrophy of the heart :
RAS activating ligand/RAS activating receptor complex (IGF1_HBEGF_LIF_ALOX15B_CTF1)
→
SHC/GRB2/SOS-1 complex (SOS1-GRB2-SHC1)
(modification, activates)
-
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 Plasma membrane estrogen receptor signaling:
IGF1 (IGF1)
→
E2/ER alpha (dimer)/PELP1/Src/p52 SHC complex (ESR1-PELP1-SRC-SHC1)
(modification, collaborate)
Kahlert et al., J Biol Chem 2000, Song et al., Proc Natl Acad Sci U S A 2004
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database Plasma membrane estrogen receptor signaling:
E2/ER alpha (dimer)/PELP1/Src/p52 SHC complex (ESR1-PELP1-SRC-SHC1)
→
IGF-1R heterotetramer/IGF1 complex (IGF1R-IGF1)
(modification, activates)
Kahlert et al., J Biol Chem 2000, Song et al., Proc Natl Acad Sci U S A 2004
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database IGF1 pathway:
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc complex (IGF1R-IGF1-GRB2-SHC1-SOS1)
→
HRAS/GTP complex (HRAS)
(modification, activates)
-
NCI Pathway Database IGF1 pathway:
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc complex (IGF1R-IGF1-GRB2-SHC1-SOS1)
→
HRAS/GDP complex (HRAS)
(modification, activates)
-
NCI Pathway Database IGF1 pathway:
IGF-1R heterotetramer/IGF1 complex (IGF1R-IGF1)
→
IGF-1R heterotetramer/IGF1/SHC/GRB10 complex (IGF1R-IGF1-SHC1-GRB10)
(modification, collaborate)
Morrione et al., Cancer Res 1996*, Dey et al., Mol Endocrinol 1996, O'Neill et al., J Biol Chem 1996, He et al., J Biol Chem 1998
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database IGF1 pathway:
IGF-1R heterotetramer/IGF1 complex (IGF1R-IGF1)
→
SHC (SHC1)
(modification, collaborate)
Morrione et al., Cancer Res 1996*, Dey et al., Mol Endocrinol 1996, O'Neill et al., J Biol Chem 1996, He et al., J Biol Chem 1998
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database IGF1 pathway:
GRB10 (GRB10)
→
IGF-1R heterotetramer/IGF1/SHC/GRB10 complex (IGF1R-IGF1-SHC1-GRB10)
(modification, collaborate)
Morrione et al., Cancer Res 1996*, Dey et al., Mol Endocrinol 1996, O'Neill et al., J Biol Chem 1996, He et al., J Biol Chem 1998
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database IGF1 pathway:
IGF-1R heterotetramer/IGF1/SHC/GRB10 complex (IGF1R-IGF1-SHC1-GRB10)
→
SHC (SHC1)
(modification, collaborate)
Morrione et al., Cancer Res 1996*, Dey et al., Mol Endocrinol 1996, O'Neill et al., J Biol Chem 1996, He et al., J Biol Chem 1998
Evidence: mutant phenotype, assay, physical interaction
-
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/GRB2/Sos/Shc complex (IGF1R-IGF1-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 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 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 IGF1 pathway:
GRB2/SOS1/SHC complex (GRB2-SOS1-SHC1)
→
IGF-1R heterotetramer/IGF1 complex (IGF1R-IGF1)
(modification, collaborate)
-
NCI Pathway Database IGF1 pathway:
GRB2/SOS1/SHC complex (GRB2-SOS1-SHC1)
→
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc complex (IGF1R-IGF1-GRB2-SHC1-SOS1)
(modification, collaborate)
-
NCI Pathway Database IGF1 pathway:
IGF-1R heterotetramer/IGF1 complex (IGF1R-IGF1)
→
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc complex (IGF1R-IGF1-GRB2-SHC1-SOS1)
(modification, collaborate)
-
Reactome Reaction:
IGF1
→
SHC1
(indirect_complex)
Hernández-Sánchez et al., J Biol Chem 1995*, Tartare-Deckert et al., J Biol Chem 1995*, Giorgetti et al., Eur J Biochem 1994*, Kim et al., J Biol Chem 1998
-
Reactome Reaction:
IGF1
→
SHC1
(reaction)
Hernández-Sánchez et al., J Biol Chem 1995*, Tartare-Deckert et al., J Biol Chem 1995*, Giorgetti et al., Eur J Biochem 1994*, Kim et al., J Biol Chem 1998
Text-mined interactions from Literome
Soon et al., Mol Cell Biol 1999
:
Grb2 association with
SHC and mitogen activated protein kinase ( MAPK ) activity was also enhanced in
response to
IGF-I stimulation
Ariga et al., Biochem J 2000
:
We found that the
IGF-I dependent tyrosine phosphorylation of 66 kDa
Shc ( Src homology collagen ) was markedly increased by cAMP pretreatment, and that this change was mainly due to an increase in the levels of 66 kDa Shc protein ... Under these conditions, cAMP pretreatment significantly increased binding of Grb2 ( growth-factor-receptor bound protein 2 ) to
Shc in
response to
IGF-I , and activation of MAP kinase ( mitogen activated protein kinase ) induced by IGF-I was also enhanced by cAMP
Hermanto et al., Mol Cell Biol 2002
:
While
IGF-I induced
activation of IRS-1,
Shc , PI3K, and MAPK pathways was unaffected, IGF-I-inducible beta1 integrin associated kinase activity and association of Crk with p130 ( CAS ) were significantly inhibited by RACK1 overexpression
Mincione et al., Exp Cell Res 2003
:
Conversely, TGF-beta 1 did not alter IGF-I stimulated IRS-1 associated phosphatidylinositol 3-kinase activity,
IGF-I induced tyrosine phosphorylation of
Shc , and its binding to Grb2
Biedi et al., Endocrinology 2003
:
Here we show that
IGF-I induces
Shc tyrosine phosphorylation in the caveolae with a time course significantly different from that observed in the nonraft cellular fractions
Panetta et al., Biochem Biophys Res Commun 2004
:
Recently, we have demonstrated that
IGF-I could specifically
regulate Shc phosphorylation in caveolae
Wadsworth et al., Endocrinology 2004
:
There was no effect on
IGF-I induced phosphorylation of MAPK, IGF-IR, or
Shc
Xin et al., Am J Physiol Gastrointest Liver Physiol 2004
(Crohn Disease) :
Immunoprecipitation studies demonstrated that
IGF-I stimulation
resulted in tyrosine phosphorylation of IRS-1, IRS-2, and
Shc
Vincent et al., Neurobiol Dis 2004
:
IGF-I :
IGF-IR signaling
involves phosphorylation of IRS-1 and
Shc , but not IRS-2
Kiely et al., J Biol Chem 2005
:
Shc was not phosphorylated in
response to
IGF-I in cells expressing the Y1250F/Y1251F mutant and remained associated with protein phosphatase 2A
Maile et al., Mol Endocrinol 2006
:
In the presence of this antibody,
IGF-I stimulated
Shc phosphorylation and ERK 1/2 activation were impaired, and this was associated with an inhibition in the ability of IGF-I to stimulate an increase in migration or proliferation ... This was associated with a loss of
IGF-I stimulated
Shc phosphorylation and impaired smooth muscle cell proliferation in response to IGF-I
Lieskovska et al., J Biol Chem 2006
(MAP Kinase Signaling System) :
Our previous studies have shown that
IGF-I induced
Shc phosphorylation is necessary for sustained activation of MAPK and increased cell proliferation of SMCs, and both Shc and the tyrosine phosphatase SHP-2 must be recruited to the membrane protein SHPS-1 in order for Shc to be phosphorylated ... These studies were undertaken to determine whether Src kinase activity is required to phosphorylate
Shc in
response to
IGF-I in SMC and because SHP-2 binds to Src whether their interaction was also required for IGF-I stimulated mitogenesis ... Our results show that
IGF-I induces activation of Src kinase and that is
required for
Shc phosphorylation and for optimal MAPK activation ... SMCs expressing an SHP-2 mutant that had the polyproline-rich region of SH2 deleted ( SHP-2Delta10 ) had disrupted SHP-2/Src association, impaired
IGF-I dependent
Shc phosphorylation, and an attenuated mitogenic response
Maile et al., Endocrinology 2007
(Hyperglycemia) :
IGF-I stimulated an increase in
Shc phosphorylation and enhanced activation of the MAPK pathway in SMCs grown in 25 mM glucose, whereas in cells maintained in 5 mM glucose, IGF-I had no effect on Shc phosphorylation, and the MAPK response to IGF-I was markedly reduced ... The addition of these alphaVbeta3 ligands to SMCs grown in 5 mM glucose was sufficient to permit
IGF-I stimulated
Shc phosphorylation and downstream signaling ... Because we have shown previously that alphaVbeta3 ligand occupancy is required for
IGF-I stimulated
Shc phosphorylation and stimulation of SMC growth, our data are consistent with a model in which 25 mM glucose stimulates increases in the concentrations of these extracellular matrix proteins, thus enhancing alphaVbeta3 ligand occupancy, which leads to increased Shc phosphorylation and enhanced cell migration and proliferation in response to IGF-I
Clemmons et al., Growth Horm IGF Res 2007
(Hyperglycemia) :
With hyperglycemia there is a marked increased in alphaVbeta3 ligands and
Shc phosphorylation in
response to
IGF-I is sustained
Salani et al., Endocrinology 2008
:
These results demonstrate that : 1 ) Cav-1 down-regulation negatively affects IGF-IR tyrosine phosphorylation ; 2 ) this effect causes a reduced activation of insulin receptor substrate-1,
Shc , and Akt ; and 3 ) Cav-1 is
involved in
IGF-IR antiapoptotic signaling after serum deprivation
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
Radhakrishnan et al., J Biol Chem 2010
(MAP Kinase Signaling System) :
These cultures showed reduced SHPS-1 phosphorylation, transfer of SHP-2 to SHPS-1, and impaired
Shc and MAPK phosphorylation and cell proliferation in
response to
IGF-I
Tartare-Deckert et al., J Biol Chem 1995
:
Our findings can be summarized as follows : ( i ) the tyrosine kinase activity of the
IGF-IR is
essential for the interaction with
p52Shc and IRS-1, ( ii ) p52Shc and IRS-1 bind to the IGF-IR in the NPEY-juxtamembrane motif, ( iii ) contrary to p52Shc, IRS-1 binds also to the major autophosphorylation sites ( Tyr-1131, -1135, and -1136 ) of the IGF-IR, and ( iv ) the amino-terminal domain of p52Shc is required for its association with the IR and the IGF-IR
Giorgetti et al., Eur J Biochem 1994
:
Here we approached the insulin induced and the insulin-like-growth-factor-I induced ( IGF-I induced ) phosphorylation of
SHC proteins, and the possible
role of these proteins in insulin and
IGF-I signaling
Sasaoka et al., Endocrinology 1996
:
Insulin and
IGF-1 stimulated tyrosine phosphorylation of IRS-1 and
Shc in a similar dose- and time dependent manner
Esposito et al., Endocrinology 1997
(Cell Transformation, Neoplastic) :
IGF-I stimulated autophosphorylation of the IGF-IR and tyrosine phosphorylation of IRS-1 and
SHC , known substrates in the IGF-IR signal transduction pathway, were studied
Chow et al., J Biol Chem 1998
:
A mutation in the C terminus of the IGF-I receptor decreased both the rate of receptor internalization and
IGF-I stimulated
Shc phosphorylation by more than 50 %, but did not affect IRS-1 phosphorylation
Kim et al., J Biol Chem 1998
(Neuroblastoma) :
Insulin receptor substrate 2 and
Shc play different roles in
insulin-like growth factor I signaling ... In the current study, we report that
IGF-I induces a sustained tyrosine phosphorylation of
Shc and its association with Grb2 in SH-SY5Y human neuroblastoma cells