ATP-independent activation of natriuretic peptide receptors

Laura K. Antos, Sarah E. Abbey-Hosch, Darcy R. Flora, Lincoln R. Potter

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Natriuretic peptide receptor A (NPR-A) is an essential cardiovascular regulator that is stimulated by atrial natriuretic peptide and B-type natriuretic peptide, whereas natriuretic peptide receptor B (NPR-B) stimulates long bone growth in a C-type natriuretic peptide-dependent manner. Many reports indicate that ATP is essential for NPR-A and NPR-B activation. Current models suggest that natriuretic peptide binding to receptor extracellular domains causes ATP binding to intracellular kinase homology domains, which derepresses adjacent catalytic domains. Here, we report 100-fold activations of natriuretic peptide receptors in the absence of ATP. The addition of a nonhydrolyzable ATP analog had no effect at early time periods (measured in seconds) but increased cGMP production about 2-fold after longer incubations (measured in minutes), consistent with a stabilization, not activation, mechanism. These data indicate that ATP does not activate natriuretic peptide receptors as has been repeatedly reported. Instead, ATP increases activity primarily by maintaining proper receptor phosphorylation status but also serves a previously unappreciated enzyme stabilizing function.

Original languageEnglish (US)
Pages (from-to)26928-26932
Number of pages5
JournalJournal of Biological Chemistry
Volume280
Issue number29
DOIs
StatePublished - Jul 22 2005

Fingerprint

Natriuretic Peptides
Peptide Receptors
Adenosine Triphosphate
Chemical activation
C-Type Natriuretic Peptide
Phosphorylation
Brain Natriuretic Peptide
Bone Development
Atrial Natriuretic Factor
Catalytic Domain
Bone
Phosphotransferases
Stabilization
Enzymes

Cite this

ATP-independent activation of natriuretic peptide receptors. / Antos, Laura K.; Abbey-Hosch, Sarah E.; Flora, Darcy R.; Potter, Lincoln R.

In: Journal of Biological Chemistry, Vol. 280, No. 29, 22.07.2005, p. 26928-26932.

Research output: Contribution to journalArticle

Antos, Laura K. ; Abbey-Hosch, Sarah E. ; Flora, Darcy R. ; Potter, Lincoln R. / ATP-independent activation of natriuretic peptide receptors. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 29. pp. 26928-26932.
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