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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2012
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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. |
format | Online Article Text |
id | pubmed-3442408 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
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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