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Research ArticlePERSPECTIVES IN PHARMACOLOGY

Post-Translational Control of Endothelial Nitric Oxide Synthase: Why Isn't Calcium/Calmodulin Enough?

David Fulton, Jean-Philippe Gratton and William C. Sessa
Journal of Pharmacology and Experimental Therapeutics December 2001, 299 (3) 818-824;
David Fulton
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Jean-Philippe Gratton
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William C. Sessa
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Abstract

Endothelial nitric oxide synthase (eNOS) is important for cardiovascular homeostasis, vessel remodeling, and angiogenesis. Given the impact of endothelium- derived nitric oxide (NO) in vascular biology, much work in the past several years has focused on the control of NO synthesis by regulatory proteins that influence its function. Indeed calcium-activated calmodulin is important for regulation of NOS activity. Herein we discuss why other proteins, in addition to calmodulin, are necessary for eNOS regulation and summarize the biology of negative and positive regulators of eNOS function in vitro, in cells, and in blood vessels.

Footnotes

  • This work is supported by grants from the National Institutes of Health (RO1 HL57665, HL61371, and HL64793 to W.C.S.; T32HL10183 to D.F.) and a Grant-in-Aid from the American Heart Association (National Grant to W.C.S.). J.P.G. is the recipient of a fellowship from the Canadian Institutes of Health Research. W.C.S. is an Established Investigator of the American Heart Association.

  • Abbreviations:
    NO
    nitric oxide
    eNOS
    endothelial NO synthase
    ACh
    acetylcholine
    B2
    bradykinin 2
    CaM
    calmodulin
    Erk
    extracellular signal-related kinase
    GA
    geldanamycin
    GST
    glutathioneS-transferase
    hsp90
    heat shock protein 90
    ID4
    intracellular domain 4
    IGF
    insulin-like growth factor
    NOSIP
    nitric oxide synthase interacting protein
    PI-3K
    phosphatidylinositol 3-kinase
    VEGF
    vascular endothelial growth factor
    • Received February 2, 2001.
    • Accepted May 25, 2001.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 299 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 299, Issue 3
1 Dec 2001
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Research ArticlePERSPECTIVES IN PHARMACOLOGY

Post-Translational Control of Endothelial Nitric Oxide Synthase: Why Isn't Calcium/Calmodulin Enough?

David Fulton, Jean-Philippe Gratton and William C. Sessa
Journal of Pharmacology and Experimental Therapeutics December 1, 2001, 299 (3) 818-824;

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Research ArticlePERSPECTIVES IN PHARMACOLOGY

Post-Translational Control of Endothelial Nitric Oxide Synthase: Why Isn't Calcium/Calmodulin Enough?

David Fulton, Jean-Philippe Gratton and William C. Sessa
Journal of Pharmacology and Experimental Therapeutics December 1, 2001, 299 (3) 818-824;
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