◀ Back to IGF1
IGF1 — SRC
Pathways - manually collected, often from reviews:
-
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
Text-mined interactions from Literome
Arbet-Engels et al., J Biol Chem 1999
:
The results suggest that
c-Src and CSK are
involved in
IGF-IR and IR signaling and that the interaction of CSK with the IGF-IR may play a role in the decrease in c-Src activity following IGF-I stimulation
Tanno et al., Cancer Res 2001
(Neoplasm Invasiveness...) :
Furthermore, AKT induced
IGF-IR expression was
down-regulated by dominant negative
Src or PTEN
Sumitomo et al., Cancer Res 2001
(Prostatic Neoplasms) :
Incubation of TSU-Pr1 cells with specific kinase inhibitors together with ET-1 or bombesin showed that
IGF-IR activation is required for neuropeptide induced Akt phosphorylation, and that neuropeptide induced Akt activation is predominantly
mediated by
Src and phosphatidylinositol 3-kinase but not by mitogen activated protein kinase or protein kinase C
Hallak et al., Hepatology 2002
:
EGF stimulated the tyrosine phosphorylation of
Src , and
induced its association with the
IGF-IR
Zeng et al., Biochem Biophys Res Commun 2003
(Neoplasm Invasiveness...) :
On the other hand
Src activation through
IGF-IR is required for the cell proliferation, invasion, and also VPF/VEGF expression
Gruden et al., Kidney Int 2003
:
IGF-I induces vascular endothelial growth factor in human mesangial cells via a
Src dependent mechanism ...
IGF-I induces VEGF gene expression and protein secretion in human mesangial cells via a
Src dependent mechanism
Sekimoto et al., Endocrinology 2003
:
Src activity increased 2- to 4-fold in IGF-I stimulated proliferating cells ; however,
IGF-I had a marginal affect on Src activity in growth arrested cells and
inhibited Src activity localized at the membrane in differentiating cells ... Src activity increased 2- to 4-fold in IGF-I stimulated proliferating cells ; however,
IGF-I had a marginal affect on Src activity in growth arrested cells and
inhibited Src activity localized at the membrane in differentiating cells ... These results suggest that the loss of IGF-I downstream mitogenic signaling in differentiating 3T3-L1 cells is due to a change in
IGF-I activation of
c-Src and CSK may mediate the inactivation of c-Src by IGF-I in 3T3-L1 adipogenesis
Sekimoto et al., Mol Endocrinol 2005
:
( alpha ) v ( beta ) 3 integrins and Pyk2 mediate
insulin-like growth factor I activation of
Src and mitogen activated protein kinase in 3T3-L1 cells ...
IGF-I increased tyrosine phosphorylation of the focal adhesion kinase ( FAK ) Pyk2 ( calcium dependent proline-rich tyrosine kinase-2 ) to a much greater extent than FAK, and
increased association of
Src with Pyk2 but not FAK
Knowlden et al., Endocrinology 2005
(Breast Neoplasms) :
These results suggest the existence of a unidirectional
IGF-IR/EGFR cross-talk mechanism whereby IGF-II, acting through the IGF-IR, regulates basal and ligand activated EGFR signaling and cell proliferation in a
c-SRC dependent manner in Tam-R cells
Lieskovska et al., J Biol Chem 2006
(MAP Kinase Signaling System) :
IGF-I induced both Src/SHP-2 and
Src/SHPS-1 association ...
IGF-I induced association of
Src and SHPS-1 was also impaired in SHP-2Delata10 expressing cells, although SHP-2/SHPS-1 association was unaffected
Fleming et al., Endocrinology 2006
:
Interestingly, inhibition of
Src activation
blocked the ability of EGF, but not
IGF-I , to activate AKT
Meng et al., Free Radic Biol Med 2007
:
IGF-I stimulated ROS production and
Src activation
Di et al., Hum Reprod 2008
(Leiomyoma...) :
Additionally, extracellular regulated kinase (ERK),
Src homology/collagen (Shc) and ER alpha were transiently activated, and interactions between ER alpha and
IGF-I receptor (IGF-IR) were rapidly
induced by genistein in LM cells
Xi et al., J Biol Chem 2010
:
These studies were conducted to determine how p66 ( shc ) alters
IGF-I stimulated
Src activation, leading to decreased IGF-I actions ... Disruption of this interaction using a synthetic peptide containing the p66 ( shc ) polyproline domain or expression of a p66 ( shc ) mutant containing substitutions for the proline residues ( P47A/P48A/P50A ) resulted in enhanced
Src kinase activity, p52 ( shc ) phosphorylation, MAPK activation, and cell proliferation in
response to
IGF-I
Carver et al., J Biol Chem 2010
(Breast Neoplasms) :
Src family kinase activity was
required for IGF-IR association with SHP-2, ligand induced IGF-IR internalization, and PRL enhanced
IGF-IR phosphorylation
Shen et al., Cell Mol Life Sci 2010
(MAP Kinase Signaling System) :
In vascular smooth muscle cells,
IGF-I stimulates
SHPS-1/SHP2/Src complex formation which is required for IGF-I stimulated cell proliferation ... Pyk2 recruitment to SHPS-1 is mediated via the interaction of Pyk2 Tyr402 and the
Src in
response to
IGF-I
Shen et al., J Biol Chem 2010
:
A proline-rich sequence in PDK1 bound to an
Src homology 3 domain in Grb2 in
response to
IGF-I
Xi et al., Diabetes 2012
(Hyperglycemia) :
Hyperglycemia enhances
IGF-I stimulated
Src activation via increasing Nox4 derived reactive oxygen species in a PKC? dependent manner in vascular smooth muscle cells ...
IGF-I stimulated
sarcoma viral oncogene (Src) activation during hyperglycemia is required for propagating downstream signaling ... The aim of the current study was to determine the mechanism by which hyperglycemia enhances
IGF-I stimulated
Src activation and the role of NADPH oxidase 4 (Nox4) and protein kinase C ? ( PKC? ) in mediating this response in vascular smooth muscle cells ( VSMCs ) ... The role of Nox4 derived reactive oxygen species ( ROS ) in
IGF-I stimulated
Src activation was investigated via knockdown of Nox4 ... Knockdown of Nox4 prevented ROS generation and impaired the oxidation and activation of
Src in
response to
IGF-I , whereas knockdown of Nox1 had no effect ... Nox4 derived ROS is responsible for the enhancing effect of hyperglycemia on
IGF-I stimulated
Src activation, which in turn amplifies IGF-I linked downstream signaling and biological actions
Trerotola et al., J Cell Physiol 2012
(Prostatic Neoplasms) :
These enhanced
Src and FAK activities are not
mediated by changes in either the activity of
IGF-IR , which is known to bind RACK1, or IGF-IR 's ability to associate with ß ( 1 ) integrins
Fujita et al., J Biol Chem 2013
:
Inhibitors of IGF1R,
Src , AKT, and ERK1/2 did not
suppress avß3-IGF-IGF1R ternary complex formation, suggesting that activation of these kinases are not required for ternary complex formation
Xi et al., J Biol Chem 2013
(Diabetes Mellitus, Experimental) :
Recruitment of Nox4 to a plasma membrane scaffold is required for localized reactive oxygen species generation and sustained
Src activation in
response to
insulin-like growth factor-I ... Nox4 derived ROS is increased in response to hyperglycemia and is required for
IGF-I stimulated
Src activation ...
IGF-I stimulated sustained
Src activation, which occurred primarily on the SHPS-1 scaffold protein