Guanylyl Cyclase C
Guanylyl cyclase C (GC-C) is the target for a family of heat-stable enterotoxins (ST) produced by enterotoxigenic Escherichia coli (ETEC), Vibrio cholera non-01, and Yersinia enterocolitica. Stable toxin-mediated diarrheas are observed frequently in infants and contribute significantly to incidences of Travelers’ Diarrhea. Early studies demonstrated that the effects of ST were mediated by increases in intracellular cGMP levels in intestinal cells, and the receptor for ST was almost exclusively expressed in the apical microvillar compartment of the intestinal brush-border epithelia (De Jonge 1975; Schulz et al. 1990). Subsequently, the receptor for ST peptides was identified as a member of the membrane-associated guanylyl cyclase family, and binding of ST to GC-C led to activation of the receptor, resulting in the production and accumulation of cGMP in enterocytes (Schulz et al. 1990). Effectors of cGMP in intestinal cells...
- Bakre MM, Sopory S, Visweswariah SS. Expression and regulation of the cGMP-binding, cGMP-specific phosphodiesterase (PDE5) in human colonic epithelial cells: role in the induction of cellular refractoriness to the heat-stable enterotoxin peptide. J Cell Biochem. 2000;77:159–67.PubMedCrossRefGoogle Scholar
- Chen T, Kocinsky HS, Cha B, Murtazina R, Yang J, Tse CM, et al. Cyclic GMP kinase II (cGKII) inhibits NHE3 by altering its trafficking and phosphorylating NHE3 at three required sites identification of a multifunctional phosphorylation site. J Biol Chem. 2015;290(4):1952–65.PubMedCrossRefGoogle Scholar