Background：

Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1).Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involved in cell growth and survival control. IGF1R is crucial for tumor transformation and survival of malignant cell. Ligand binding activates the receptor kinase， leading to receptor autophosphorylation， and tyrosines phosphorylation of multiple substrates， that function as signaling adapter proteins including， the insulin-receptor substrates (IRS1/2)， Shc and 14-3-3 proteins. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway and the Ras-MAPK pathway. The result of activating the MAPK pathway is increased cellular proliferation， whereas activating the PI3K pathway inhibits apoptosis and stimulates protein synthesis. Phosphorylated IRS1 can activate the 85 kDa regulatory subunit of PI3K (PIK3R1)， leading to activation of several downstream subst