Natriuretic peptide signalling: Molecular and cellular pathways to growth regulation

Michael Silberbach, Charles T. Roberts

Research output: Contribution to journalReview articlepeer-review

183 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)221-231
Number of pages11
JournalCellular Signalling
Issue number4
StatePublished - 2001


  • Atrial natriuretic peptide
  • Cardiac hyperthrophy
  • Guanylyl cyclase
  • PKG

ASJC Scopus subject areas

  • Cell Biology


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