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

Barbara Schroeder, Subhashini Srivatsan, Andrey Shaw, Daniel Billadeau, Mark A. McNiven

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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 oc curs. 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 sequestra tion of the ubiquitinated receptor into multivesicular bodies (MVBs) for subsequent degrada tion. These findings provide novel insights into how src- kinase-based regulation of a cbl adaptor regulates the fate of the EGFR.

Original languageEnglish (US)
Pages (from-to)3602-3611
Number of pages10
JournalMolecular biology of the cell
Volume23
Issue number18
DOIs
StatePublished - Sep 15 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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