Question

Hello, I need help in regards to cell signalling and insulin signalling pathways. the question asks:

1) Describe the steps between the binding of an insulin molecule at the surface of the target cell and the activation of the effector PI3K.

Answer 1

the insulin receptor (INS-R) is a receptor tyrosine kinase. it consists of two alpha subunits on the outer face of the plasma membrane and two transmembrane beta subunits. binding of insulin to the alpha subunits triggers a conformational change that allows the autophosphorylation of tyrosine residues in the carboxy terminal domain of the beta subunits. the phosphorylated insulin receptor next phosphorylates insulin recpetor substrates (IRS) on tyrosine residues. phosphorylated IRS binds to the SH2 domains of a variety of proteins that are directly involved in mediating different effects of insulin .

phosphorylated IRS molecule act as a docking site for enzyme PI-3 kinase that leads to the activation of PKB(also called Akt) . the activated PKB phosphorylates glycogen synthase kinase 3 (GSK3) and inactivate it. inactivation of GSK3 makes glycogen synthase active which accelerates the synthesis of glycogen from glucose. in muscle and fat tissue, PKB also triggers the movemment of glucose transporters (GLUT4) from internal vesicles to the plasma membrane, stimulating glucose uptake from the blood.

IRS -1 , phosphorylated by the insulin receptor, activates PI-3K by binding to its SH2 domain.PI-3K converts PIP2 to PIP3. -----> PKB bound to PIP3 phosphorylated by PDK1. thus activated, PKB phosphorylates GSK3 on a Ser residue, inactvating it.-----> GSK3 , inactivated by phosphorylation, cannot convert glycogen synthase to its inactive form by phosphoryation-----> synthesis of glycogen from glucose is accelerated.