Shear stress stimulates phosphorylation of eNOS at Ser635by a protein kinase A-dependent mechanism
| Autor: | Jinah Hwang, Bruce E. Kemp, Michelle C. Sykes, Hazel Lum, Belinda J. Michell, Hanjoong Jo, Yong Chool Boo |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Threonine
Vascular Endothelial Growth Factor A medicine.medical_specialty Nitric Oxide Synthase Type III Physiology 8-Bromo Cyclic Adenosine Monophosphate Aorta Thoracic Endothelial Growth Factors Protein Serine-Threonine Kinases Biology Wortmannin chemistry.chemical_compound Enos Proto-Oncogene Proteins Physiology (medical) Internal medicine Cyclic AMP Serine medicine Animals Phosphorylation Protein kinase A Cells Cultured Lymphokines Vascular Endothelial Growth Factors Kinase biology.organism_classification Cyclic AMP-Dependent Protein Kinases Cell biology Nitric oxide synthase Endothelial stem cell Vascular endothelial growth factor A Endocrinology chemistry biology.protein Intercellular Signaling Peptides and Proteins Cattle Endothelium Vascular Stress Mechanical Nitric Oxide Synthase Cardiology and Cardiovascular Medicine Proto-Oncogene Proteins c-akt |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 283:H1819-H1828 |
| ISSN: | 1522-1539 0363-6135 |
| Popis: | Shear stress stimulates nitric oxide (NO) production by phosphorylating endothelial NO synthase (eNOS) at Ser1179in a phosphoinositide-3-kinase (PI3K)- and protein kinase A (PKA)-dependent manner. The eNOS has additional potential phosphorylation sites, including Ser116, Thr497, and Ser635. 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 Ser635, which was consistently slower than that at Ser1179. Thr497was rapidly dephosphorylated by 8-BRcAMP but not by shear and VEGF. None of the stimuli phosphorylated Ser116. Whereas shear-stimulated Ser635phosphorylation 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 Ser635may play an important role in chronic regulation of eNOS in response to mechanical and humoral stimuli. |
| Databáze: | OpenAIRE |
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