Dynamic activation of endothelial nitric oxide synthase by Hsp90

Guillermo García-Cardeña, Roger Fan, Vijay Shah, Raffaella Sorrentino, Giuseppe Cirino, Andreas Papapetropoulos, William C. Sessa

Research output: Contribution to journalArticle

804 Citations (Scopus)

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 known. 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.

Original languageEnglish (US)
Pages (from-to)821-824
Number of pages4
JournalNature
Volume392
Issue number6678
DOIs
StatePublished - Apr 23 1998
Externally publishedYes

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HSP90 Heat-Shock Proteins
Nitric Oxide Synthase Type III
Nitric Oxide
Molecular Chaperones
Protein Folding
GTP-Binding Proteins
Histamine
Vascular Endothelial Growth Factor A
Endothelium
Blood Vessels
Intercellular Signaling Peptides and Proteins
Proteins

ASJC Scopus subject areas

  • General

Cite this

García-Cardeña, G., Fan, R., Shah, V., Sorrentino, R., Cirino, G., Papapetropoulos, A., & Sessa, W. C. (1998). Dynamic activation of endothelial nitric oxide synthase by Hsp90. Nature, 392(6678), 821-824. https://doi.org/10.1038/33934

Dynamic activation of endothelial nitric oxide synthase by Hsp90. / García-Cardeña, Guillermo; Fan, Roger; Shah, Vijay; Sorrentino, Raffaella; Cirino, Giuseppe; Papapetropoulos, Andreas; Sessa, William C.

In: Nature, Vol. 392, No. 6678, 23.04.1998, p. 821-824.

Research output: Contribution to journalArticle

García-Cardeña, G, Fan, R, Shah, V, Sorrentino, R, Cirino, G, Papapetropoulos, A & Sessa, WC 1998, 'Dynamic activation of endothelial nitric oxide synthase by Hsp90', Nature, vol. 392, no. 6678, pp. 821-824. https://doi.org/10.1038/33934
García-Cardeña G, Fan R, Shah V, Sorrentino R, Cirino G, Papapetropoulos A et al. Dynamic activation of endothelial nitric oxide synthase by Hsp90. Nature. 1998 Apr 23;392(6678):821-824. https://doi.org/10.1038/33934
García-Cardeña, Guillermo ; Fan, Roger ; Shah, Vijay ; Sorrentino, Raffaella ; Cirino, Giuseppe ; Papapetropoulos, Andreas ; Sessa, William C. / Dynamic activation of endothelial nitric oxide synthase by Hsp90. In: Nature. 1998 ; Vol. 392, No. 6678. pp. 821-824.
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