AMP-activated protein kinase phosphorylation of endothelial NO synthase

FEBS Lett. 1999 Jan 29;443(3):285-9. doi: 10.1016/s0014-5793(98)01705-0.

Abstract

The AMP-activated protein kinase (AMPK) in rat skeletal and cardiac muscle is activated by vigorous exercise and ischaemic stress. Under these conditions AMPK phosphorylates and inhibits acetyl-coenzyme A carboxylase causing increased oxidation of fatty acids. Here we show that AMPK co-immunoprecipitates with cardiac endothelial NO synthase (eNOS) and phosphorylates Ser-1177 in the presence of Ca2+-calmodulin (CaM) to activate eNOS both in vitro and during ischaemia in rat hearts. In the absence of Ca2+-calmodulin, AMPK also phosphorylates eNOS at Thr-495 in the CaM-binding sequence, resulting in inhibition of eNOS activity but Thr-495 phosphorylation is unchanged during ischaemia. Phosphorylation of eNOS by the AMPK in endothelial cells and myocytes provides a further regulatory link between metabolic stress and cardiovascular function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AMP-Activated Protein Kinases
  • Amino Acid Sequence
  • Animals
  • Aorta
  • Calmodulin / metabolism
  • Cattle
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / enzymology*
  • Enzyme Activation
  • Kinetics
  • Liver / enzymology
  • Molecular Sequence Data
  • Multienzyme Complexes / metabolism*
  • Myocardial Ischemia / enzymology
  • Myocardium / enzymology
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type III
  • Phosphorylation
  • Precipitin Tests
  • Protein Binding
  • Protein Kinases / metabolism*
  • Protein-Serine-Threonine Kinases*
  • Rats
  • Recombinant Proteins / metabolism
  • Serine / metabolism
  • Threonine / metabolism

Substances

  • Calmodulin
  • Multienzyme Complexes
  • Recombinant Proteins
  • Threonine
  • Serine
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • AMP-Activated Protein Kinases