Domain analysis of human transmembrane guanylyl cyclase receptors: implications for regulation.
In the human genome, sequence analysis indicates there are five functional transmembrane guanylyl cyclases, enzymes that synthesize the intracellular second messenger, cGMP. Two, GC-A and GC-B or NPR-A and NPR-B, are widely distributed receptors for atrial natriuretic peptide, brain natriuretic peptide and C-type natriuretic peptide, more commonly known as ANP, BNP and CNP, respectively. One cyclase, GC-C or StaR, is predominantly found in the intestinal epithelium and is the receptor for guanylin and uroguanylin, as well as for the bacterial pathogen, heat-stable enterotoxin (Sta). The remaining two cyclases, GC-E and GC-F or RetGC-1 and RetGC-2, are expressed in the retina and regulate the dark cycle of phototransduction. Unlike the other family members, GC-E and GC-F have no known extracellular ligands. Instead, they are activated under low calcium conditions by guanylyl cyclase activating proteins called GCAPs. All five members consist of an extracellular ligand binding domain, single transmembrane spanning domain, and intracellular kinase homology, dimerization and guanylyl cyclase catalytic domains. In the first part of this review, the tissue expression, ligands and "knockout" phenotypes of each receptor are summarized and individual domains are compared. In the second part, regulation by ATP, calcium, protein kinase C and phosphorylation is discussed.
Potter
Lincoln Ross
LR
Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, 6-155 Jackson Hall, 321 Church Street, S. E., Minneapolis, USA. potter@umn.edu
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002384:Catalysis; D019281:Dimerization; D006162:Guanylate Cyclase / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D011493:Protein Kinase C / Q000378:metabolism*; D017434:Protein Structure, Tertiary
D008565:Membrane Proteins; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D006162:Guanylate Cyclase; D002118:Calcium