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Record 20 of 941
Shear stress stimulates phosphorylation of eNOS at Ser(635) by a protein kinase A-dependent mechanism
External Online Source: doi:10.1152/ajpheart.00214.2002
Author and Affiliation:
Boo, Yong Chool(Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Atlanta, GA 30322, United States)
Hwang, Jinah
Sykes, Michelle
Michell, Belinda J.
Kemp, Bruce E.
Lum, Hazel
Jo, Hanjoong
Abstract: Shear stress stimulates nitric oxide (NO) production by phosphorylating endothelial NO synthase (eNOS) at Ser(1179) in a phosphoinositide-3-kinase (PI3K)- and protein kinase A (PKA)-dependent manner. The eNOS has additional potential phosphorylation sites, including Ser(116), Thr(497), and Ser(635). Here, we studied these potential phosphorylation sites in response to shear, vascular endothelial growth factor (VEGF), and 8-bromocAMP (8-BRcAMP) in bovine aortic endothelial cells (BAEC). All three stimuli induced phosphorylation of eNOS at Ser(635), which was consistently slower than that at Ser(1179). Thr(497) was rapidly dephosphorylated by 8-BRcAMP but not by shear and VEGF. None of the stimuli phosphorylated Ser(116). Whereas shear-stimulated Ser(635) phosphorylation was not affected by phosphoinositide-3-kinase inhibitors wortmannin and LY-294002, it was blocked by either treating the cells with a PKA inhibitor H89 or infecting them with a recombinant adenovirus-expressing PKA inhibitor. These results suggest that shear stress stimulates eNOS by two different mechanisms: 1) PKA- and PI3K-dependent and 2) PKA-dependent but PI3K-independent pathways. Phosphorylation of Ser(635) may play an important role in chronic regulation of eNOS in response to mechanical and humoral stimuli.
Publication Date: Nov 01, 2002
Document ID:
20040088037
(Acquired Sep 07, 2004)
Subject Category: LIFE SCIENCES (GENERAL)
Document Type: Journal Article
Publication Information: American journal of physiology. Heart and circulatory physiology (ISSN 0363-6135); Volume 283; 5; H1819-28
Publisher Information: United States
Contract/Grant/Task Num: HL 60905
Description: In English
Distribution Limits: Unclassified; Publicly available; Unlimited
Rights: Copyright
NASA Terms: ENDOTHELIUM; ENZYMES; PHOSPHORYLATION; PROTEINS; SHEAR STRESS; ADENOSINE MONOPHOSPHATE; AMINO ACIDS; AORTA; CATTLE; CULTURED CELLS; CYCLIC AMP; CYTOLOGY; NUCLEOTIDES; ONCOGENES; STRESSES
Other Descriptors: CYCLIC AMP-DEPENDENT PROTEIN KINASES/METABOLISM; ENDOTHELIUM, VASCULAR/CYTOLOGY/ENZYMOLOGY; NITRIC-OXIDE SYNTHASE/METABOLISM; 8-BROMO CYCLIC ADENOSINE MONOPHOSPHATE/PHARMACOLOGY; ANIMALS; AORTA, THORACIC/CYTOLOGY; CATTLE; CELLS, CULTURED; CYCLIC AMP/PHARMACOLOGY; ENDOTHELIAL GROWTH FACTORS/PHARMACOLOGY; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS/PHARMACOLOGY; LYMPHOKINES/PHARMACOLOGY; PHOSPHORYLATION/DRUG EFFECTS; PROTO-ONCOGENE PROTEINS/METABOLISM; SERINE/METABOLISM; STRESS, MECHANICAL; SUPPORT, NON-U.S. GOV'T; SUPPORT, U.S. GOV'T, NON-P.H.S; SUPPORT, U.S. GOV'T, P.H.S; THREONINE/METABOLISM; VASCULAR ENDOTHELIAL GROWTH FACTOR A; VASCULAR ENDOTHELIAL GROWTH FACTORS; NASA DISCIPLINE CELL BIOLOGY; NON-NASA CENTER
Availability Source: Other Sources
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