Fig. 2.

IGF-1R kinase-dependent signaling pathways. IGF-1 (or IGF-2) binding to the IGF-1R promotes intrinsic tyrosine kinase activity and auto-phosphorylation. Activated receptor can recruit and phosphorylate substrates such as IRS and Shc. Tyrosine phosphorylation of IRS and Shc proteins leads to binding of signaling molecules such as Grb2 and PI 3-kinase. These associations induce downstream signaling activation, primarily through the MAPK and PI3K pathways coordinating downstream IGFs bioactivities