Phosphorylation of atrial natriuretic peptides by cyclic AMP-dependent protein kinase

J. Rittenhouse, L. Moberly, Martha E O'Donnell, N. E. Owen, F. Marcus

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Atrial natriuretic peptides refer to a family of related peptides secreted by atria that appear to have an important role in the control of blood pressure. The structure of these peptides shows the amino acid sequence Arg101-Arg102-Ser103-Ser104, which is a typical recognition sequence (Arg-Arg-X-Ser) for phosphorylation by cyclic AMP-dependent protein kinase. With this background, we tested two synthetic atrial natriuretic peptides (Arg101-Tyr126 and Gly96-Tyr126) as substrates for in vitro phosphorylation by the catalytic subunit of cyclic AMP-dependent protein kinase. The tested atrial natriuretic peptides were found to be substrates for the reaction. Sequence studies demonstrated that the site of phosphorylation was located, as expected, at Ser104. Kinetic studies demonstrate that both atrial natriuretic peptides are excellent substrates for cyclic AMP-dependent protein kinase. In particular, the longer peptide Gly96-Tyr126 exhibited an apparent K(m) value of about 0.5 μM, to our knowledge the lowest reported K(m) for a cyclic AMP-dependent protein kinase substrate. Preliminary studies to measure the biological activity of the in vitro phosphorylated atrial peptides indicate that these compounds are more effective than the corresponding dephospho forms in stimulating Na/K/Cl cotransport in cultured vascular smooth muscle cells.

Original languageEnglish (US)
Pages (from-to)7607-7610
Number of pages4
JournalJournal of Biological Chemistry
Volume261
Issue number17
StatePublished - 1986
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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