Cyclic nucleotide dependent phosphorylation of neuronal nitric oxide synthase inhibits catalytic activity

J. L. Dinerman, J. P. Steiner, T. M. Dawson, V. Dawson, S. H. Snyder

Research output: Contribution to journalArticle

Abstract

We have examined the regulation of neuronal nitric oxide synthase (NOS) by phosphorylation with cyclic-GMP (PKG) and cyclic-AMP-dependent (PKA) protein kinases. In vitro phosphorylation studies indicate that both PKG and PKA phosphorylate NOS on a single site. Phosphoamino-acid analysis and peptide mapping demonstrate that phosphorylation by either cyclic-nucleotide kinase occurs on a similar serine residue. Phosphorylation of purified NOS by either PKG or PKA diminishes catalytic activity. Stimulation by 8-Br-cGMP of HEK-293 cells stably transfected with the cDNA for neuronal NOS (293.NOS cells) results in phosphorylation of immunoprecipitated NOS. Incubation of 293-NOS cells with 8-bromo-cGMP or dibutyryl-cAMP reduces nitrite release in response to stimulation with calcium ionophore A23187. Phosphorylation-induced decreases in NOS activity may counterbalance and modulate NOS activating signals.

Original languageEnglish (US)
Pages (from-to)1245-1251
Number of pages7
JournalNeuropharmacology
Volume33
Issue number11
DOIs
StatePublished - Nov 1994

Keywords

  • Nitric oxide
  • nitric oxide synthase
  • phosphorylation
  • protein kinases

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Cyclic nucleotide dependent phosphorylation of neuronal nitric oxide synthase inhibits catalytic activity'. Together they form a unique fingerprint.

  • Cite this