AMP‐activated protein kinase phosphorylation of endothelial NO synthase

FEBS Letters

Mitchelhill, Ken I³  Power, David A¹  Witters, Lee A⁴  Michell, Belinda J³  Rodriguez-Crespo, Ignacio²  Chen, Zhi-Ping³  Stapleton, David³  Kemp, Bruce E³  Ortiz de Montellano, Paul R² 

[1] Department of Clinical Immunology, St. Vincent's Hospital, 41 Victoria Parade, Fitzroy, Vic. 3065, Australia;Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, CA 94143-0446, USA;St. Vincent's Institute of Medical Research, St. Vincent's Hospital, 41 Victoria Parade, Fitzroy, Vic. 3065, Australia;Endocrine-Metabolism Division, Departments of Medicine and Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA

关键词: AMP-activated protein kinase;    Endothelial NO synthase;    Cardiac;    Ischaemia;   

DOI  :  10.1016/S0014-5793(98)01705-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown