Identifiers
NAME:IGF family*:IGF1R
Maps_Modules
HMC:ACTIVATING_INVASION_AND_METASTASIS
EMT Senescence / EMT_REGULATORS
EMT Senescence / ECM
References
PMID:12175651
PMID:10826997
PMID:12767520
PMID:19030972
PMID:16931767
PMID:21540285
PMID:12444011
em_emtc_emtc_re1272( EMT Senescence ):
PMID:17673906
Upon TGFB stimulation, the activated TGFBR1 recruits and directly phosphorylates SHC1 on tyrosine and serine.
TGFB-induced SHC1 phosphorylation induces SHC1 association with Grb2 and Sos
Upon IGF stimulation, the activated IGF1R recruits and directly phosphorylates SHC1, leading to cellular proliferation
em_emtc_emtc_re1609( EMT Senescence ):
Upon IGF stimulation, the activated IGF1R recruits and directly phosphorylates IRS1, leading to both PI3K and (GRB2/SOS/HRas) pathways activation
em_emtc_emtc_re1618( EMT Senescence ):
IGFfamily exhibits anti-apoptotic activity.
Three IGF1R-induced anti-apoptotic pathways:
1. IRS1-mediated pathway causing activation of PI3K and AKT(PKB) leading to BAD phosphorylation.
Unphosphorylated BAD, by binding to BCLXL and BCL2, neutralizes the protective effect of these 2 later proteins and promotes cell death.
Phosphorylated BAD is sequestered by 14-3-3 protein family and thus unable to bind BCL2 family hence can not promote cell death.
2. After autophosphorylation and thus activation, IGF1R binds and postively influence on 14-3-3 protein family, leading to activation and translocation of c-Raf1 to the mitochondria where it phosphorylates BAD.
3. IGF1R specifically phosphorylates and inhibits ASK1 (MAP3K5)
em_emtc_emtc_re1621( EMT Senescence ):
PMID:11274345
PMID:12655147
ASK1 is a MAP3K and can activate both JNK and P38 pathways.
TNF-dependent production of ROS triggers the dissociation of Trx from ASK1 and the consequently liberalised ASK1 binds to TRAF2. Finally TRAF2 appears to activate ASK1 (by phosphorylation) by enhancing and stabilising the oligomerisation of ASK1.
PMID:12556535
IGF1R signaling suppresses the ASK1-mediated stimulation of JNK/p38 thus supresses the induction of apoptosis.
Identifiers
NAME:IGF family*:IGF1R
Maps_Modules
HMC:ACTIVATING_INVASION_AND_METASTASIS
EMT Senescence / EMT_REGULATORS
EMT Senescence / ECM
References
PMID:12175651
PMID:10826997
PMID:12767520
PMID:19030972
PMID:16931767
PMID:21540285
PMID:12444011