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CIN85 phosphorylation is essential for EGFR ubiquitination and sorting into multivesicular bodies

Ubiquitination of the epidermal growth factor receptor (EGFR) by cbl and its cognate adaptor cbl-interacting protein of 85 kDa (CIN85) is known to play an essential role in directing this receptor to the lysosome for degradation. The mechanisms by which this ubiquitin modification is regulated are n...

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Autores principales: Schroeder, Barbara, Srivatsan, Subhashini, Shaw, Andrey, Billadeau, Daniel, McNiven, Mark A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3442408/
https://www.ncbi.nlm.nih.gov/pubmed/22833562
http://dx.doi.org/10.1091/mbc.E11-08-0666
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author Schroeder, Barbara
Srivatsan, Subhashini
Shaw, Andrey
Billadeau, Daniel
McNiven, Mark A.
author_facet Schroeder, Barbara
Srivatsan, Subhashini
Shaw, Andrey
Billadeau, Daniel
McNiven, Mark A.
author_sort Schroeder, Barbara
collection PubMed
description Ubiquitination of the epidermal growth factor receptor (EGFR) by cbl and its cognate adaptor cbl-interacting protein of 85 kDa (CIN85) is known to play an essential role in directing this receptor to the lysosome for degradation. The mechanisms by which this ubiquitin modification is regulated are not fully defined, nor is it clear where this process occurs. In this study we show that EGFR activation leads to a pronounced src-mediated tyrosine phosphorylation of CIN85 that subsequently influences EGFR ubiquitination. Of importance, phospho-CIN85 interacts with the Rab5-positive endosome, where it mediates the sequestration of the ubiquitinated receptor into multivesicular bodies (MVBs) for subsequent degradation. These findings provide novel insights into how src- kinase–based regulation of a cbl adaptor regulates the fate of the EGFR.
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spelling pubmed-34424082012-11-30 CIN85 phosphorylation is essential for EGFR ubiquitination and sorting into multivesicular bodies Schroeder, Barbara Srivatsan, Subhashini Shaw, Andrey Billadeau, Daniel McNiven, Mark A. Mol Biol Cell Articles Ubiquitination of the epidermal growth factor receptor (EGFR) by cbl and its cognate adaptor cbl-interacting protein of 85 kDa (CIN85) is known to play an essential role in directing this receptor to the lysosome for degradation. The mechanisms by which this ubiquitin modification is regulated are not fully defined, nor is it clear where this process occurs. In this study we show that EGFR activation leads to a pronounced src-mediated tyrosine phosphorylation of CIN85 that subsequently influences EGFR ubiquitination. Of importance, phospho-CIN85 interacts with the Rab5-positive endosome, where it mediates the sequestration of the ubiquitinated receptor into multivesicular bodies (MVBs) for subsequent degradation. These findings provide novel insights into how src- kinase–based regulation of a cbl adaptor regulates the fate of the EGFR. The American Society for Cell Biology 2012-09-15 /pmc/articles/PMC3442408/ /pubmed/22833562 http://dx.doi.org/10.1091/mbc.E11-08-0666 Text en © 2012 Schroeder 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 BD; are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Schroeder, Barbara
Srivatsan, Subhashini
Shaw, Andrey
Billadeau, Daniel
McNiven, Mark A.
CIN85 phosphorylation is essential for EGFR ubiquitination and sorting into multivesicular bodies
title CIN85 phosphorylation is essential for EGFR ubiquitination and sorting into multivesicular bodies
title_full CIN85 phosphorylation is essential for EGFR ubiquitination and sorting into multivesicular bodies
title_fullStr CIN85 phosphorylation is essential for EGFR ubiquitination and sorting into multivesicular bodies
title_full_unstemmed CIN85 phosphorylation is essential for EGFR ubiquitination and sorting into multivesicular bodies
title_short CIN85 phosphorylation is essential for EGFR ubiquitination and sorting into multivesicular bodies
title_sort cin85 phosphorylation is essential for egfr ubiquitination and sorting into multivesicular bodies
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3442408/
https://www.ncbi.nlm.nih.gov/pubmed/22833562
http://dx.doi.org/10.1091/mbc.E11-08-0666
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