C-type natriuretic peptide and guanylyl cyclase B receptor.
Guanylyl cyclases (GC) are widely distributed enzymes that signal via the production of the second messenger cGMP. The particulate guanylyl cyclases share a similar topology: an extracellular ligand binding domain and intracellular regulatory kinase-homology and cyclase catalytic domains. The natriuretic peptide receptors GC-A and -B mediate the effects of a family of peptides, atrial, B- and C-type natriuretic peptide (ANP, BNP and CNP, respectively), with natriuretic, diuretic and vasorelaxant properties. ANP and BNP, through the activation of GC-A, act as endocrine hormones to regulate blood pressure and volume, and inhibit cardiac hypertrophy. CNP, on the other hand, acts in an autocrine/paracrine fashion to induce vasorelaxation and vascular remodeling, and to regulate bone growth through its cognate receptor GC-B. GC-B, like GC-A, is phosphorylated in the basal state, and undergoes both homologous and heterologous desensitization, reflected by dephosphorylation of specific sites in the kinase-homology domain. This review will examine the structure and function of GC-B, and summarize the physiological processes in which this receptor is thought to participate.
Schulz
Stephanie
S
Division of Clinical Pharmacology, Department of Medicine and Biochemistry, Thomas Jefferson University, Philadelphia, PA 19107, USA. stephanie.schulz@jefferson.edu
D000818:Animals; D001794:Blood Pressure; D001842:Bone and Bones / Q000378:metabolism; D002319:Cardiovascular System; D049109:Cell Proliferation; D002490:Central Nervous System; D006162:Guanylate Cyclase / Q000502:physiology*; D006801:Humans; D006984:Hypertrophy; D008024:Ligands; D008954:Models, Biological; D020098:Natriuretic Peptide, C-Type / Q000502:physiology*; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D017461:Receptors, Atrial Natriuretic Factor / Q000502:physiology*; D013329:Structure-Activity Relationship; D000099242:Atrial Natriuretic Factor Receptor B
D006162:Guanylate Cyclase; D008024:Ligands; D020098:Natriuretic Peptide, C-Type; D017461:Receptors, Atrial Natriuretic Factor; D000099242:Atrial Natriuretic Factor Receptor B