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Dynamic activation of endothelial nitric oxide synthase by Hsp90

Author

Listed:
  • Guillermo García-Cardeña

    (Department of Pharmacology and Molecular Cardiobiology Program
    Brigham and Women's Hospital)

  • Roger Fan

    (Department of Pharmacology and Molecular Cardiobiology Program)

  • Vijay Shah

    (Boyer Center for Molecular Medicine, Yale University School of Medicine)

  • Raffaella Sorrentino

    (Universita' degli Studi di Napoli Federico II)

  • Giuseppe Cirino

    (Universita' degli Studi di Napoli Federico II)

  • Andreas Papapetropoulos

    (Department of Pharmacology and Molecular Cardiobiology Program)

  • William C. Sessa

    (Department of Pharmacology and Molecular Cardiobiology Program)

Abstract

Heat-shock protein 90 (Hsp90) coordinates the trafficking and regulation of diverse signalling proteins, but its precise role in regulating specific cellular targets is not known1,2. Here we show that Hsp90 associates with endothelial nitric oxide synthase (eNOS) and is rapidly recruited to the eNOS complex by agonists that stimulate production of nitric oxide, namely vascular endothelial growth factor, histamine and fluid shear stress. Moreover, the binding of Hsp90 to eNOS enhances the activation of eNOS. Inhibition of signalling through Hsp90 attenuates both agonist-stimulated production of nitric oxide and endothelium-dependent relaxation of isolated blood vessels. Our results indicate that Hsp90 facilitates signalling mediated by growth-factor, G-protein and mechanotransduction pathways that lead to the activation of eNOS. These observations indicate that in addition to its role as a molecular chaperone involved in protein folding and maturation, Hsp90 may also be recruited to cellular targets depending on the activation state of the cell.

Suggested Citation

  • Guillermo García-Cardeña & Roger Fan & Vijay Shah & Raffaella Sorrentino & Giuseppe Cirino & Andreas Papapetropoulos & William C. Sessa, 1998. "Dynamic activation of endothelial nitric oxide synthase by Hsp90," Nature, Nature, vol. 392(6678), pages 821-824, April.
    • Handle: RePEc:nat:nature:v:392:y:1998:i:6678:d:10.1038_33934
    DOI: 10.1038/33934
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    Cited by:

    1. Yan Zhao & Liju Tao & Dongpo Jiang & Xingyun Chen & Ping Li & Yalei Ning & Renping Xiong & Ping Liu & Yizhi Peng & Yuan-Guo Zhou, 2013. "The -144C/A Polymorphism in the Promoter of HSP90beta Is Associated with Multiple Organ Dysfunction Scores," PLOS ONE, Public Library of Science, vol. 8(3), pages 1-7, March.
    2. Roberta d'Emmanuele di Villa Bianca & Emma Mitidieri & Ferdinando Fusco & Elena D'Aiuto & Paolo Grieco & Ettore Novellino & Ciro Imbimbo & Vincenzo Mirone & Giuseppe Cirino & Raffaella Sorrentino, 2012. "Endogenous Urotensin II Selectively Modulates Erectile Function through eNOS," PLOS ONE, Public Library of Science, vol. 7(2), pages 1-6, February.

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