The pathogen, Vibrio cholera, secretes cholera toxin, which in turn leads to G-protein-mediated activation of adenylate cyclase in intestinal enterocytes, resulting in massive elevation in the kinase activity of protein kinase A (PKA). The phosphorylation of which of the following proteins, by PKA, results in the induction of watery diarrhea in individuals infected with this pathogen?

Question

Quizplus · Accepted Answer

PKA phosphorylates the plasma membrane chloride channel, specifically the CFTR channel, leading to increased chloride ion secretion into the intestinal lumen, which causes watery diarrhea. The toxin protein from Vibrio cholera catalyzes the ADP ribosylation of the α-subunit of G_s G-proteins in the intestines. The ADP ribosylation causes the G_as subunit to lose its catalytic activity in hydrolyzing GTP, so it remains activated longer than normal. Increased G_as activation leads to increased adenylate cyclase activity, which increases the intracellular concentration of cAMP to more than 100-fold over the normal and overactivates PKA. The activated PKA then phosphorylates the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel proteins, which leads to ATP-mediated efflux of chloride ions and leads to secretion of H₂O and other ions into the intestinal lumen.

The Pathogen, Vibrio Cholera, Secretes Cholera Toxin, Which in Turn