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

Publication Type:

Journal Article


Molecular biology of the cell (2012)


Ubiquitination of the epidermal growth factor receptor (EGFR) by cbl and its cognate adaptor CIN85 (cbl interacting protein of 85 kDa) is known to play an essential role in directing this receptor to the lysosome for degradation. Currently, 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. Importantly, 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.