Insulin-stimulated phosphorylation of endothelial nitric oxide synthase at serine-615 contributes to nitric oxide synthesis

Biochemical Journal

Volumn 426, Issue 1, 2010, Pages 85-90

  Ritchie, Stuart A ^a,b   Kohlhaas, Christine F ^a   Boyd, Alasdair R ^a   Yalla, Krishna C ^a   Walsh, Kenneth ^c   Connell, John M C ^b   Salt, Ian P ^a  

^a UNIVERSITY OF GLASGOW   (United Kingdom)

^b UNIVERSITY OF GLASGOW   (United Kingdom)

^c BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Endothelial nitric oxide synthase (eNOS); Endothelium; Insulin; Nitric oxide; Phosphorylation; Protein kinase B (PKB); Signalling

Indexed keywords

ASPARTIC ACIDS; DOMINANT-NEGATIVE MUTANTS; ENDOTHELIAL NITRIC OXIDE SYNTHASE; ENDOTHELIAL NITRIC OXIDE SYNTHASE (ENOS); ENDOTHELIUM; GLUCOSE CONCENTRATION; HUMAN AORTIC ENDOTHELIAL CELLS; NECROSIS FACTORS; PARALLEL MECHANISMS; PHOSPHOINOSITIDE 3-KINASE; PRE-INCUBATION; PROTEIN KINASE B; SYNTHASES; WORTMANNIN;

AMINO ACIDS; BLOOD VESSEL PROSTHESES; CELL CULTURE; ENDOTHELIAL CELLS; GENE EXPRESSION; GLUCOSE; INSULIN; MECHANISMS; NITRIC OXIDE; ORGANIC ACIDS; PHOSPHATASES; PROTEINS; SELF ASSEMBLY; TUMORS;

PHOSPHORYLATION;

ADENOVIRUS VECTOR; ALANINE; ASPARTIC ACID; ENDOTHELIAL NITRIC OXIDE SYNTHASE; GLUCOSE; INSULIN; NITRIC OXIDE; PHENFORMIN; PROTEIN KINASE B; SERINE; TUMOR NECROSIS FACTOR ALPHA; WORTMANNIN; ANTIDIABETIC AGENT;

AMINO ACID SUBSTITUTION; ARTICLE; CONTROLLED STUDY; DOWN REGULATION; ENDOTHELIUM CELL; HUMAN; HUMAN CELL; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; BIOSYNTHESIS; CELL CULTURE; DRUG EFFECT; GENETICS; HELA CELL; METABOLISM; PHOSPHORYLATION; POLYACRYLAMIDE GEL ELECTROPHORESIS; SITE DIRECTED MUTAGENESIS; WESTERN BLOTTING;

BLOTTING, WESTERN; CELLS, CULTURED; ELECTROPHORESIS, POLYACRYLAMIDE GEL; HELA CELLS; HUMANS; HYPOGLYCEMIC AGENTS; INSULIN; MUTAGENESIS, SITE-DIRECTED; NITRIC OXIDE; NITRIC OXIDE SYNTHASE TYPE III; PHOSPHORYLATION; SERINE;

EID: 76549129255     PISSN: 02646021     EISSN: 14708728     Source Type: Journal    
DOI: 10.1042/BJ20091580     Document Type: Article

References (26)

1. Potenza, M. A., Gagliardi, S., Nacci, C., Carratu', M. R. and Montagnani, M. (2009) Endothelial dysfunction in diabetes: from mechanisms to therapeutic targets. Curr. Med. Chem. 16, 94-112
2. Potenza, M. A., Addabbo, F. and Montagnani, M. (2009) Vascular actions of insulin with implications for endothelial dysfunction. Am. J. Physiol. Endocrinol. Metab. 297, E568-E577
3. Steinberg, H. O., Brechtel, G., Johnson, A., Fineberg, N. and Baron, A. D. (1994) Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. J. Clin. Invest. 94, 1172-1174
4. Ueda, S., Petrie, J. R., Cleland, S. J., Elliott, H. L. and Connell, J. M. (1998) The vasodilating effect of insulin is dependent on local glucose uptake: a double blind, placebo-controlled study. J. Clin. Endocrinol. Metab. 83, 2126-2131
5. Zeng, G. and Quon, M. J. (1996) Insulin-stimulated production of nitric oxide is inhibited by wortmannin. Direct measurement in vascular endothelial cells. J. Clin. Invest. 98, 894-898
6. Salt, I. P., Morrow, V. A., Brandie, F. M., Connell, J. M. C. and Petrie, J. R. (2003) High glucose inhibits insulin-stimulated nitric oxide production without reducing eNOS Ser1177 phosphorylation in human aortic endothelial cells. J. Biol. Chem. 278, 18791-18797
7. Kim, F., Gallis, B. and Corson, M. A. (2001) TNF-α inhibits flow and insulin signaling leading to NO production in aortic endothelial cells. Am. J. Physiol. Cell Physiol. 280, C1057-C1065
8. Mount, P. F., Kemp, B. E. and Power, D. A. (2007) Regulation of endothelial and myocardial NO synthesis by multi-site eNOS phosphorylation. J. Mol. Cell. Cardiol. 42, 271-279
9. Bauer, P. M., Fulton, D., Boo, Y. C., Sorescu, G. P., Kemp, B. E., Jo, H. and Sessa, W. C. (2003) Compensatory phosphorylation and protein-protein interactions revealed by loss of function and gain of function mutants of multiple serine phosphorylation sites in endothelial nitric-oxide synthase. J. Biol. Chem. 278, 14841-14849
10. Michell, B, J., Harris, M.B., Chen, Z.P., Ju, H., Venema, V.J., Blackstone, M.A., Huang, W., Venema, R, C. and Kemp, B. E. (2002) Identification of regulatory sites of phosphorylation of the bovine endothelial nitric-oxide synthase at serine 617 and serine 635. J. Biol. Chem. 277, 42344-42351
11. Harris, M. B., Blackstone, M. A., Sood, S. G., Li, C., Goolsby, J. M., Venema, V. J., Kemp, B. E. and Venema, R. C. (2004) Acute activation and phosphorylation of endothelial nitric oxide synthase by HMG-CoA reductase inhibitors. Am. J. Physiol. Heart Circ. Physiol. 287, H560-H566
12. Boyle, J. G., Logan, P. J., Ewart, M. A., Reihill, J. A., Ritchie, S. A., Connell, J. M. C., Cleland, S. J. and Salt, I. P. (2008) Rosiglitazone stimulates nitric oxide synthesis in human aortic endothelial cells via AMP-activated protein kinase. J. Biol. Chem. 283, 11210-11217
13. Reihill, J. A., Ewart, M. A., Hardie, D. G. and Salt, I. P. (2007) AMP-activated protein kinase mediates VEGF-stimulated endothelial NO production. Biochem. Biophys. Res. Commun. 354, 1084-1088
14. Luo, Z., Fujio, Y., Kureishi, Y., Rudic, R. D., Daumerie, G., Fulton, D., Sessa, W. C. and Walsh, K. (2000) Acute modulation of endothelial Akt/PKB activity alters nitric oxide-dependent vasomotor activity in vivo. J. Clin. Invest. 106, 493-499
15. Morrow, V. A., Foufelle, F., Connell, J. M. C., Petrie, J. R., Gould, G. W. and Salt, I. P. (2003) Direct activation of AMP-activated protein kinase stimulates nitric-oxide synthesis in human aortic endothelial cells. J. Biol. Chem. 278, 31629-31639
16. Aljada, A., Ghanim, H., Assian, E. and Dandona, P. (2002) Tumor necrosis factor-α inhibits insulin-induced increase in endothelial nitric oxide synthase and reduces insulin receptor content and phosphorylation in human aortic endothelial cells. Metabolism 51, 487-491
17. Li, C., Harris, M. B., Venema, V. J. and Venema, R. C. (2005) Endostatin induces acute endothelial nitric oxide and prostacyclin release. Biochem. Biophys. Res. Commun. 329, 873-878
18. 2+) values for calmodulin binding and enzyme activation. J. Biol. Chem. 284, 11892-11899
19. Li, C., Ruan, L., Sood, S. G., Papapetropoulos, A., Fulton, D. and Venema, R. C. (2007) Role of eNOS phosphorylation at Ser-116 in regulation of eNOS activity in endothelial cells. Vasc. Pharmacol. 47, 257-264
20. Church, J. E. and Fulton, D. (2006) Differences in eNOS activity because of subcellular localisation are dictated by phosphorylation state rather than the local calcium environment. J. Biol. Chem. 281, 1477-1488
21. Federici, M., Pandolfi, A., De Filippis, E. A., Pellegrini, G., Menghini, R., Lauro, D., Cardellini, M., Romano, M., Sesti, G., Lauro, R. and Consoli, A. (2004) G972R IRS-1 variant impairs insulin regulation of endothelial nitric oxide synthase in cultured human endothelial cells. Circulation 109, 399-405
22. Andreozzi, F., Laratta, E., Procopio, C., Hribal, M. L., Sciacqua, A., Perticone, M., Miele, C., Perticone, F. and Sesti, G. (2007) Interleukin-6 impairs the insulin signalling pathway, promoting production of nitric oxide in human umbilical vein endothelial cells. Mol. Cell. Biol. 27, 2372-2383
23. Kou, R., Greif, D. and Michel, T. (2002) Dephosphorylation of endothelial nitric-oxide synthase by vascular endothelial growth factor: implications for the vascular responses to cyclosporin A. J. Biol. Chem. 277, 29669-29673
24. Gallis, B., Corthals, G. L., Goodlett, D. R., Ueba, H., Kim, F., Presnell, S. R., Figeys, D., Harrison, D. G., Berk, B. C., Aebersold, R. and Corson, M. A. (1999) Identification of flow-dependent endothelial nitric-oxide synthase phosphorylation sites by mass spectrometry and regulation of phosphorylation and nitric oxide production by the phosphatidylinositol 3-kinase inhibitor LY294002. J. Biol. Chem. 274, 30101-30108
25. Takahashi, S. and Mendelsohn, M. E. (2003) Synergistic activation of endothelial nitric-oxide synthase (eNOS) by HSP90 and Akt: calcium-independent eNOS activation involves formation of an HSP90-Akt-CaM-bound eNOS complex. J. Biol. Chem. 278, 30821-30827
26. Repetto, S., Salani, B., Maggi, D. and Cordera, R. (2005) Insulin and IGF-I phosphorylate eNOS in HUVECs by a caveolin-1 dependent mechanism. Biochem. Biophys. Res. Commun. 337, 849-852