Humans express four soluble (α1, γ2, α1, γ2) guanylyl cyclase subunits and five single membrane-spanning (GC-A, GC-B, GC-C, GC-E, and GC-F) forms. The soluble forms exist as heterodimers and the transmembrane members exist as homeric structures containing at least two molecules per complex. The primary and best-studied endogenous activator of soluble guanylyl cyclase (sGC) is nitric oxide (NO) originally described as endothelium-derived relaxing factor for its potent ability to relax blood vessels in response to vasodilators such as acetylcholine or bradykinin. The transmembrane guanylyl cyclases are homodimers that are activated by peptides. The best-characterized transmembrane guanylyl cyclase is NPR-A, which is also called GC-A or NPR1. It binds and is activated by atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP). NPR-A is phosphorylated on four serines and two threonines within the amino-terminal portion of its kinase homology domain in the unstimulated state. The natriuretic peptide clearance receptor, which is also called NPR-C or NPR3, shares 35 percent amino acid identity with NPR-A and NPR-B in its extracellular domain, and binds all three known natriuretic peptides with similar affinities. It also binds osteocrin, which acts a decoy ligand to increase CNP levels in bone tissue. NPR-C is expressed in most tissues, usually at levels that are significantly higher than those of NPR-A or NPR-B. NPR-B, which is also called GC-B or NPR2, has a similar topology to NPR-A but is activated by CNP, which exists in 22 and 53 amino acid forms, neither of which are stored in granules. CNP does not circulate at high levels; rather, it signals in a paracrine manner.
|Original language||English (US)|
|Title of host publication||Handbook of Cell Signaling, 2/e|
|Number of pages||9|
|State||Published - 2010|
Bibliographical noteFunding Information:
The article is dedicated to the memory of Dr David L. Garbers, who made repeated seminal contributions to the guanylyl cyclase field during his distinguished career. I thank Dr Deborah Dickey for critically reading the manuscript. Research in Dr Potter’s laboratory is supported by grants from the National Institutes of Health, the American Heart Association, Minnesota Medical Foundation, and a Medica funded Minnesota-Mayo Partnership Grant.