In a comparative study of 2 related cell lines, you find that one responds normally to insulin while the other has an impaired response. You discover that both cell lines bind insulin with equal affinity, but that the impaired response is manifest in an inability to recruit the insulin response substrate-1 (IRS-1) protein to the receptor. This would most likely be due to which of the following?
A) inability of the receptor to phosphorylate the RAS G-protein
B) loss of activation of phospholipase C-β (PLC-β)
C) mutation in the tyrosine phosphate recognition site of IRS-1
D) serine phosphorylation of the insulin receptor preventing IRS-1 binding
E) tyrosine phosphorylation of the insulin receptor, leading to the loss of the IRS-1-binding site

Question

Quizplus · Accepted Answer

A mutation in the tyrosine phosphate recognition site of IRS-1 would prevent IRS-1 from being recruited to the insulin receptor, leading to an impaired insulin response despite normal insulin binding.  Binding of insulin to its receptors triggers activation of the intrinsic tyrosine kinase activity of the receptor. In addition to the incorporation of phosphate on tyrosine residues of several target proteins, the receptor autophosphorylates tyrosine residues on itself. These receptor-associated tyrosine phosphates serve as docking site for several signaling proteins including IRS-1. A loss in the ability of IRS-1 to bind to the phosphorylated tyrosine due to a mutation in the recognition motif would impair insulin-mediated signaling through IRS-1.

In a Comparative Study of 2 Related Cell Lines, You