RGD Reference Report - Atrial natriuretic peptide induces natriuretic peptide receptor-cGMP-dependent protein kinase interaction. - Rat Genome Database

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Atrial natriuretic peptide induces natriuretic peptide receptor-cGMP-dependent protein kinase interaction.

Authors: Airhart, N  Yang, YF  Roberts CT, JR  Silberbach, M 
Citation: Airhart N, etal., J Biol Chem. 2003 Oct 3;278(40):38693-8. Epub 2003 Jul 10.
RGD ID: 1580152
Pubmed: PMID:12855709   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M304098200   (Journal Full-text)

Circulating natriuretic peptides such as atrial natriuretic peptide (ANP) counterbalance the effects of hypertension and inhibit cardiac hypertrophy by activating cGMP-dependent protein kinase (PKG). Natriuretic peptide binding to type I receptors (NPRA and NPRB) activates their intrinsic guanylyl cyclase activity, resulting in a rapid increase in cytosolic cGMP that subsequently activates PKG. Phosphorylation of the receptor by an unknown serine/threonine kinase is required before ligand binding can activate the cyclase. While searching for downstream PKG partners using a yeast two-hybrid screen of a human heart cDNA library, we unexpectedly found an upstream association with NPRA. PKG is a serine/threonine kinase capable of phosphorylating NPRA in vitro; however, regulation of NPRA by PKG has not been previously reported. Here we show that PKG is recruited to the plasma membrane following ANP treatment, an effect that can be blocked by pharmacological inhibition of PKG activation. Furthermore, PKG participates in a ligand-dependent gain-of-function loop that significantly increases the intrinsic cyclase activity of the receptor. PKG translocation is ANP-dependent but not nitric oxide-dependent. Our results suggest that anchoring of PKG to NPRA is a key event after ligand binding that determines distal effects. As such, the NPRA-PKG association may represent a novel mechanism for compartmentation of cGMP-mediated signaling and regulation of receptor sensitivity.

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
sarcolemma located_inIDA 1580152 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Prkg1  (protein kinase cGMP-dependent 1)

Objects referenced in this article
Gene Npr1 natriuretic peptide receptor 1 Rattus norvegicus

Additional Information