Natriuretic peptide signalling: molecular and cellular pathways to growth regulation.
The natriuretic peptides (NPs) constitute a family of polypeptide hormones that regulate mammalian blood volume and blood pressure. The ability of the NPs to modulate cardiac hypertrophy and cell proliferation as well is now beginning to be recognized. The NPs interact with three membrane-bound receptors, all of which contain a well-characterized extracellular ligand-binding domain. The R1 subclass of NP receptors (NPR-A and NPR-B) contains a C-terminal guanylyl cyclase domain and is responsible for most of the NPs downstream actions through their ability to generate cGMP. The R2 subclass lacks an obvious catalytic domain and functions primarily as a clearance receptor. This review focuses on the signal transduction pathways initiated by ligand binding and other factors that help to determine signalling specificities, including allosteric factors modulating cGMP generation, receptor desensitization, the activation and function of cGMP-dependent protein kinase (PKG), and identification of potential nuclear or cytoplasmic targets such as the mitogen-activated protein kinase signalling (MAPK) cascade. The inhibition of cardiac growth and hypertrophy may be an important but underappreciated action of the NP signalling system.
Silberbach
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Division of Pediatric Cardiology, Department of Pediatrics, Doernbecher Children's Hospital, UHN-60, 3181 SW Sam Jackson Park Road, 97201, Portland, OR, USA. silberbm@ohsu.edu
Roberts
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CT
D000595:Amino Acid Sequence; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D020134:Catalytic Domain; D002455:Cell Division; D006152:Cyclic GMP / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D003593:Cytoplasm / Q000201:enzymology; D006162:Guanylate Cyclase / Q000737:chemistry; D006801:Humans; D006984:Hypertrophy; D008024:Ligands; D020935:MAP Kinase Signaling System; D008954:Models, Biological; D008969:Molecular Sequence Data; D020097:Natriuretic Peptide, Brain / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017461:Receptors, Atrial Natriuretic Factor / Q000737:chemistry; D015398:Signal Transduction
D008024:Ligands; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A; D006152:Cyclic GMP