Insulin, being a growth factor, increases the rate of protein synthesis, in part, by increasing the activity of the kinase mTOR. Activation of mTOR in response to insulin receptor stimulation requires inhibition of which of the following upstream signaling molecules?
A) AMPK
B) GSK3
C) PKB/Akt
D) PI3K
E) TSC1/TSC2

Question

Quizplus · Accepted Answer

TSC1/TSC2 complex acts as a negative regulator of mTOR. Insulin signaling inhibits TSC1/TSC2, leading to activation of mTOR.  Insulin action leads to an increase in the activity of PI3K which in turn phosphorylates membrane phospholipids generating PIP3 which then activates PDK1 which in turn phosphorylates and activates PKB/Akt. Activated PKB/Akt will phosphorylate TSC2 (tuberin) of the TSC1/TSC2 complex resulting in altered activity of the complex. The TSC1/TSC2 complex functions as a GTPase-activating protein (GAP) which increases GTP hydrolyzing activity of Rheb. The faster the GTPase action of Rheb the faster will be the reduction in Rheb activation of mTOR. When TSC1/TSC2 is phosphorylated by PKB it is less effective at stimulating the GTPase activity of Rheb and, therefore Rheb activation of mTOR will remain high in response to insulin action.

Insulin, Being a Growth Factor, Increases the Rate of Protein