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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2013
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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. |
format | Online Article Text |
id | pubmed-3861084 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
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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