Inhibition of PKCalpha and rhoA translocation in differentiated smooth muscle by a caveolin scaffolding domain peptide

Taggart, Michael J.;Leavis, Paul;Feron, Olivier;Morgan, Kathleen G.
(2000) Experimental Cell Research : emphasizing molecular approaches to cell biology — Vol. 258, n° 1, p. 72-81 (2000)

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  • Taggart, Michael J.
    Author
  • Leavis, Paul
    Author
  • Author
  • Morgan, Kathleen G.
    Author
Abstract
Receptor-coupled contraction of smooth muscle involves recruitment to the plasma membrane of downstream effector molecules PKC alpha and rhoA but the mechanism of this signal integration is unclear. Caveolins, the principal structural proteins of caveolar plasma membrane invaginations, have been implicated in the organization and regulation of many signal transducing molecules. Thus, using laser scanning confocal immunofluorescent microscopy, we tested the hypothesis that caveolin is involved in smooth muscle signaling by investigating caveolin isoform expression and localization, together with the effect of a peptide inhibitor of caveolin function, in intact differentiated smooth muscle cells. All three main caveolin isoforms were identified in uterine, stomach, and ileal smooth muscles and assumed a predominantly plasma membranous localization in myometrial cells. Cytoplasmic introduction of a peptide corresponding to the caveolin-1 scaffolding domain-an essential region for caveolin interaction with signaling molecules-significantly inhibited agonist-induced translocation of both PKC alpha and rhoA. Translocation was unimpaired by a scrambled peptide and was unaltered in sham-treated cells. The membranous localization of caveolins, and direct inhibition of receptor-coupled PKC alpha and rhoA translocation by the caveolin-1 scaffolding domain, supports the concept that caveolins can regulate the integration of extracellular contractile stimuli and downstream intracellular effecters in smooth muscle. (C) 2000 Academic Press.
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Taggart, M. J., Leavis, P., Feron, O., & Morgan, K. G. (2000). Inhibition of PKCalpha and rhoA translocation in differentiated smooth muscle by a caveolin scaffolding domain peptide. Experimental Cell Research : emphasizing molecular approaches to cell biology, 258(1), 72-81. https://doi.org/10.1006/excr.2000.4891 (Original work published 2000)