Identifiers
IGF family*
insulin-like growth factor 1 (somatomedin C)
HUGO:IGF1 HGNC:5464 ENTREZ:3479 UNIPROT:P05019
insulin-like growth factor 2 (somatomedin A)
HUGO:IGF2 HGNC:5466 ENTREZ:3481 UNIPROT:P01344
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
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 to 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)
IRS3 and IRS4 however have negative effect on anti-apoptotic effects of IGFR.
→ IGF1@Extracellular space
→ IGF2@Extracellular space
+ IGF family*@Extracellular space → IGF binding partners*:IGF family*@Extracellular space
+ IGF family*@Extracellular space → IGF family*:IGF1R|hm2@Cytosol
→ IGF family*:IGF1R|Y_pho|hm2@Cytosol
→ 14-3-3*@Cytosol