Threonine phosphorylation diverts internalized epidermal growth factor receptors from a degradative pathway to the recycling endosome

Article Article scientifique Article Threonine phosphorylation diverts internalized epidermal growth factor receptors from a degradative pathway to the recycling endosome eng 2000-08-25 author Bao Jing 733634 author Alroy Iris author Waterman Hadassa author Schejter Eyal author Brodie Chaya author Gruenberg Jean 29661 author Yarden Yosef 26178-26186 10.1074/jbc.M002367200 0021-9258 <p>Transregulation of the epidermal growth factor receptor (EGFR) by protein kinase C (PKC) serves as a model for heterologous desensitization of receptor tyrosine kinases, but the underlying mechanism remained unknown. By using c-Cbl-induced ubiquitination of EGFR as a marker for transfer from early to late endosomes, we provide evidence that PKC can inhibit this process. In parallel, receptor down-regulation and degradation are significantly reduced. The inhibitory effects of PKC are mediated by a single threonine residue (threonine 654) of EGFR, which serves as a major PKC phosphorylation site. Biochemical and morphological analyses indicate that threonine-phosphorylated EGFR molecules undergo normal internalization, but instead of sorting to lysosomal degradation, they recycle back to the cell surface. In conclusion, by sorting EGFR to the recycling endosome, heterologous desensitization restrains ligand-induced down-regulation of EGFR.</p> Dewey 540 39 Département de biochimie 144 false The Journal of biological chemistry 275 34 975debba-c606-4568-bba0-37af2175571b Article (Published version) Public BAO_TJBC_261862000.pdf 1751370 application/pdf CC BY openAccess Faculté des sciences / Section de chimie et biochimie / Département de biochimie

Title	Published in	Access level	OA Policy	Year	Views	Downloads

Threonine phosphorylation diverts internalized epidermal growth factor receptors from a degradative pathway to the recycling endosome	The Journal of biological chemistry			2000	271	327

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