Please use this identifier to cite or link to this item:
|Title: ||AMP-Activated Protein Kinase Functionally Phosphorylates Endothelial Nitric Oxide Synthase Ser-633.|
|Authors: ||Zhen Chen;I-Chen Peng;Wei Sun;Mei-I Su;Pang-Hung Hsu;Yi Fu, Yi Zhu;Kathryn DeFea;Songqin Pan;Ming-Daw Tsai;John Y-J. Shyy|
|Issue Date: ||2018-03-26T07:19:32Z
|Publisher: ||Circulation Research|
Endothelial nitric oxide synthase (eNOS) plays a central role in maintaining cardiovascular homeostasis by controlling NO bioavailability. The activity of eNOS in vascular endothelial cells (ECs) largely depends on posttranslational modifications, including phosphorylation. Because the activity of AMP-activated protein kinase (AMPK) in ECs can be increased by multiple cardiovascular events, we studied the phosphorylation of eNOS Ser633 by AMPK and examined its functional relevance in the mouse models. Shear stress, atorvastatin, and adiponectin all increased AMPK Thr172 and eNOS Ser633 phosphorylations, which were abolished if AMPK was pharmacologically inhibited or genetically ablated. The constitutively active form of AMPK or an AMPK agonist caused a sustained Ser633 phosphorylation. Expression of gain-/loss-of-function eNOS mutants revealed that Ser633 phosphorylation is important for NO production. The aorta of AMPKα2−/− mice showed attenuated atorvastatin-induced eNOS phosphorylation. Nano–liquid chromatography/tandem mass spectrometry (LC/MS/MS) confirmed that eNOS Ser633 was able to compete with Ser1177 or acetyl-coenzyme A carboxylase Ser79 for AMPKα phosphorylation. Nano-LC/MS/MS confirmed that eNOS purified from AICAR-treated ECs was phosphorylated at both Ser633 and Ser1177. Our results indicate that AMPK phosphorylation of eNOS Ser633 is a functional signaling event for NO bioavailability in ECs.
|Appears in Collections:||[生命科學系] 期刊論文|
Files in This Item:
All items in NTOUR are protected by copyright, with all rights reserved.