e_re1618( EMT ):
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)
Participates in complexes:
In compartment: Cytoplasm
Participates in reactions:
As Reactant or Product:
- IGF1R@Cytoplasm + IGF family*@Extracellular space → IGF family*:IGF1R|hm2@Cytoplasm
- IGF family*:IGF1R|hm2@Cytoplasm → IGF family*:IGF1R|Y_pho|hm2@Cytoplasm
- IGF family*:IGF1R|Y_pho|hm2@Cytoplasm → 14-3-3*@Cytoplasm