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Src-mediated caveolin-1 phosphorylation affects the targeting of active Src to specific membrane sites

Src interactions with the plasma membrane are an important determinant of its activity. In turn, Src activity modulates its association with the membrane through binding of activated Src to phosphotyrosylated proteins. Caveolin-1 (Cav-1), a major component of caveolae, is a known Src phosphorylation...

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Autores principales: Gottlieb-Abraham, Efrat, Shvartsman, Dmitry E., Donaldson, John C., Ehrlich, Marcelo, Gutman, Orit, Martin, G. Steven, Henis, Yoav I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3861084/
https://www.ncbi.nlm.nih.gov/pubmed/24131997
http://dx.doi.org/10.1091/mbc.E13-03-0163
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author Gottlieb-Abraham, Efrat
Shvartsman, Dmitry E.
Donaldson, John C.
Ehrlich, Marcelo
Gutman, Orit
Martin, G. Steven
Henis, Yoav I.
author_facet Gottlieb-Abraham, Efrat
Shvartsman, Dmitry E.
Donaldson, John C.
Ehrlich, Marcelo
Gutman, Orit
Martin, G. Steven
Henis, Yoav I.
author_sort Gottlieb-Abraham, Efrat
collection PubMed
description Src interactions with the plasma membrane are an important determinant of its activity. In turn, Src activity modulates its association with the membrane through binding of activated Src to phosphotyrosylated proteins. Caveolin-1 (Cav-1), a major component of caveolae, is a known Src phosphorylation target, and both were reported to regulate cell transformation. However, the nature of Src-Cav-1 interactions, a potential mechanism of their coregulation, remained unclear. Here we used fluorescence recovery after photobleaching beam-size analysis, coimmunoprecipitation, quantitative imaging, and far-Western studies with cells expressing wild type, as well as structural and activity mutants of Src–green fluorescent protein and Cav-1–monomeric red fluorescent protein, to measure their interactions with the membrane and with each other. We show dynamic Src–plasma membrane interactions, which are augmented and stabilized by Cav-1. The mechanism involves phosphorylation of Cav-1 at Tyr-14 by Src and subsequent binding of the Src SH2 domain to phospho–Cav-1, leading to accumulation of activated Src in focal adhesions. This novel Cav-1 function potentially modulates focal adhesion dynamics.
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spelling pubmed-38610842014-03-02 Src-mediated caveolin-1 phosphorylation affects the targeting of active Src to specific membrane sites Gottlieb-Abraham, Efrat Shvartsman, Dmitry E. Donaldson, John C. Ehrlich, Marcelo Gutman, Orit Martin, G. Steven Henis, Yoav I. Mol Biol Cell Articles Src interactions with the plasma membrane are an important determinant of its activity. In turn, Src activity modulates its association with the membrane through binding of activated Src to phosphotyrosylated proteins. Caveolin-1 (Cav-1), a major component of caveolae, is a known Src phosphorylation target, and both were reported to regulate cell transformation. However, the nature of Src-Cav-1 interactions, a potential mechanism of their coregulation, remained unclear. Here we used fluorescence recovery after photobleaching beam-size analysis, coimmunoprecipitation, quantitative imaging, and far-Western studies with cells expressing wild type, as well as structural and activity mutants of Src–green fluorescent protein and Cav-1–monomeric red fluorescent protein, to measure their interactions with the membrane and with each other. We show dynamic Src–plasma membrane interactions, which are augmented and stabilized by Cav-1. The mechanism involves phosphorylation of Cav-1 at Tyr-14 by Src and subsequent binding of the Src SH2 domain to phospho–Cav-1, leading to accumulation of activated Src in focal adhesions. This novel Cav-1 function potentially modulates focal adhesion dynamics. The American Society for Cell Biology 2013-12-15 /pmc/articles/PMC3861084/ /pubmed/24131997 http://dx.doi.org/10.1091/mbc.E13-03-0163 Text en © 2013 Gottlieb-Abraham et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Gottlieb-Abraham, Efrat
Shvartsman, Dmitry E.
Donaldson, John C.
Ehrlich, Marcelo
Gutman, Orit
Martin, G. Steven
Henis, Yoav I.
Src-mediated caveolin-1 phosphorylation affects the targeting of active Src to specific membrane sites
title Src-mediated caveolin-1 phosphorylation affects the targeting of active Src to specific membrane sites
title_full Src-mediated caveolin-1 phosphorylation affects the targeting of active Src to specific membrane sites
title_fullStr Src-mediated caveolin-1 phosphorylation affects the targeting of active Src to specific membrane sites
title_full_unstemmed Src-mediated caveolin-1 phosphorylation affects the targeting of active Src to specific membrane sites
title_short Src-mediated caveolin-1 phosphorylation affects the targeting of active Src to specific membrane sites
title_sort src-mediated caveolin-1 phosphorylation affects the targeting of active src to specific membrane sites
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3861084/
https://www.ncbi.nlm.nih.gov/pubmed/24131997
http://dx.doi.org/10.1091/mbc.E13-03-0163
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