AMP-activated protein kinase phosphorylation of endothelial NO synthase

• Published in: FEBS letters Vol. 443; no. 3; pp. 285 - 289
• Main Authors: Chen, Zhi-Ping, Mitchelhill, Ken I, Michell, Belinda J, Stapleton, David, Rodriguez-Crespo, Ignacio, Witters, Lee A, Power, David A, Ortiz de Montellano, Paul R, Kemp, Bruce E
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 29-01-1999
• Subjects: Amino Acid Sequence; AMP-activated protein kinase; AMP-Activated Protein Kinases; Animals; Aorta; Calmodulin - metabolism; Cardiac; Cattle; Endothelial NO synthase; Endothelium, Vascular - cytology; Endothelium, Vascular - enzymology; Enzyme Activation; Ischaemia; 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; Ischaemia; Endothelial NO synthase; AMP-activated protein kinase; Cardiac
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(98)01705-0

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 Ca
2+-calmodulin (CaM) to activate eNOS both in vitro and during ischaemia in rat hearts. In the absence of Ca
2+-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.