HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 29, 26928-26932, July 22, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/29/26928    most recent M505648200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Antos, L. K. Articles by Potter, L. R. Search for Related Content PubMed PubMed Citation Articles by Antos, L. K. Articles by Potter, L. R. Social Bookmarking                      What's this?

ATP-independent Activation of Natriuretic Peptide Receptors^*

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

From the Department of Biochemistry, Molecular Biology, and Biophysics, and ^¶Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota 55455

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.

Received for publication, May 23, 2005

^* This work was supported in part by National Institutes of Health Grant RO1HL66397 and Scientist Development Award 0130398 from the National Division of the American Heart Association (to L. R. P.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Supported by National Institutes of Health Training Grant AR07612.

^|| To whom correspondence should be addressed: 6-155 Jackson, 321 Church St. S. E., Minneapolis, MN 55455. Tel.: 612-624-7251; Fax: 612-624-7282; E-mail: potter{at}umn.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				L. K. Antos and L. R. Potter Adenine nucleotides decrease the apparent Km of endogenous natriuretic peptide receptors for GTP Am J Physiol Endocrinol Metab, December 1, 2007; 293(6): E1756 - E1763. [Abstract] [Full Text] [PDF]

				L. R. Potter, S. Abbey-Hosch, and D. M. Dickey Natriuretic Peptides, Their Receptors, and Cyclic Guanosine Monophosphate-Dependent Signaling Functions Endocr. Rev., February 1, 2006; 27(1): 47 - 72. [Abstract] [Full Text] [PDF]