Description
The insulin and IGF1 receptors are tyrosine kinases that phosphorylate various proteins, including the insulin receptor substrates Irs1 and Irs2. After insulin binds to its receptor, it activates an intrinsic tyrosine kinase activity, which mediates the tyrosine phosphorylation of a variety of endogenous substrates including insulin receptor substrates (IRS) 1 1 to 4. Binding of these tyrosine phosphorylated substrates to the Src homology (SH) domain-2 of the regulatory subunit of the heterodimeric p85/p110 phosphatidylinositol (PI) 3- kinase leads to a 3-5-fold stimulation in its enzymatic activity and an increase in the PI 3,4-bisphosphate and 3,4,5-trisphosphate in the cell. As a result of the increase in these lipids, there is a pronounced stimulation in the enzymatic activity of the Ser/Thr kinases called Akt, and a more modest increase in the enzymatic activity of particular isoforms of protein kinase C, which ultimately lead to numerous biological responses