Guanylyl cyclase structure, function and regulation

Cell Signal. 2011 Dec;23(12):1921-6. doi: 10.1016/j.cellsig.2011.09.001. Epub 2011 Sep 10.


Nitric oxide, bicarbonate, natriuretic peptides (ANP, BNP and CNP), guanylins, uroguanylins and guanylyl cyclase activating proteins (GCAPs) activate a family of enzymes variously called guanyl, guanylyl or guanylate cyclases that catalyze the conversion of guanosine triphosphate to cyclic guanosine monophosphate (cGMP) and pyrophosphate. Intracellular cyclic GMP is a second messenger that modulates: platelet aggregation, neurotransmission, sexual arousal, gut peristalsis, blood pressure, long bone growth, intestinal fluid secretion, lipolysis, phototransduction, cardiac hypertrophy and oocyte maturation. This review briefly discusses the discovery of cGMP and guanylyl cyclases, then nitric oxide, nitric oxide synthase and soluble guanylyl cyclase are described in slightly greater detail. Finally, the structure, function, and regulation of the individual mammalian single membrane-spanning guanylyl cyclases GC-A, GC-B, GC-C, GC-D, GC-E, GC-F and GC-G are described in greatest detail as determined by biochemical, cell biological and gene-deletion studies.

Publication types

  • Review

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Cyclic GMP / metabolism
  • Humans
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / chemistry
  • Nitric Oxide Synthase / metabolism
  • Protein Interaction Domains and Motifs
  • Protein Structure, Tertiary
  • Receptors, Guanylate Cyclase-Coupled / chemistry
  • Receptors, Guanylate Cyclase-Coupled / genetics
  • Receptors, Guanylate Cyclase-Coupled / metabolism*
  • Signal Transduction*


  • Nitric Oxide
  • Nitric Oxide Synthase
  • Receptors, Guanylate Cyclase-Coupled
  • Cyclic GMP