Question

Which of the following statements concerning signal transduction by the insulin receptor is NOT correct?

A. The insulin receptor substrate protein IRS-1 in its phosphorylated form activates other proteins.

B. The pathway for insulin-stimulated transcription of specific genes involves the protein Ras.

C. The insulin receptor phosphorylates itself in the activation process.

D. Insulin stimulation of the insulin receptor initiates a cascade of events causing activation of glycogen synthase.

E. The receptor protein kinase activity is specific for serine residues on the substrate proteins.

Answer 1

Incorrect option is E) The receptor protein kinase activity is specific for serine residues on the substrate proteins.

Insulin receptor is an example of receptor tyrosine kinase family. The insulin receptor protein consists of 2 alpha subunits (contain insulin binding domain) and 2 beta subunits (contain protein kinase activity). When insulin binds to receptor, it activates tyr kinase activity. Receptor undergoes autophosphorylation on its carboxy terminal Tyr residue. It then phosphorylates IRS-1 on Tyr residues. Activated IRS-1 binds to SH-2 domain of grb2 protein which then activates another protein, Ras.

IRS-1 also activates PI-3 Kinase and protein kinase B. PKB then phosphorylates Ser or Thr residue of another protein called Glycogen synthase kinase 3 (GSK-3), thus inactivating it. Activated GSK-3 (in the absence of insulin) phosphorylates glycogen synthase (which in turn helps to form glycogen from glucose) and inactivating it. But now activated insulin receptor inactivates GSK-3 by signal transduction which cannot convert glycogen synthase to its inactive form. So glycogen synthase remains active.