PMID:15475003

Citation	Grøvdal, LM, Stang, E, Sorkin, A and Madshus, IH (2004) Direct interaction of Cbl with pTyr 1045 of the EGF receptor (EGFR) is required to sort the EGFR to lysosomes for degradation. Exp. Cell Res. 300:388-95
Abstract	Mutation of the binding site for Cbl (Tyr1045) in the EGF receptor (EGFR) results in impaired ubiquitination but does not affect EGFR internalization. However, the Y1045F mutation resulted in strongly decreased degradation of the EGFR, as well as efficient recycling of EGFR to the plasma membrane. Significantly, more wild-type EGFR than Y1045F EGFR was found localizing to multivesicular late endosomes. Ubiquitination of the EGFR was in HeLa cells inhibited both upon overexpressing the N-terminal part of Cbl and upon overexpressing a double mutant Grb2 incapable of interacting with Cbl and thereby being incapable of indirectly recruiting Cbl to the EGFR. Collectively, these data suggest that the ubiquitination resulting from direct binding of Cbl to pTyr1045 of the EGFR is critical for lysosomal sorting of the EGFR in contrast to ubiquitination resulting from Grb2-mediated binding of Cbl to the EGFR.
Links	PubMed Online version:10.1016/j.yexcr.2004.07.003
Keywords	Epidermal Growth Factor/metabolism; HeLa Cells; Humans; Lysosomes/metabolism; Mutation; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-cbl; Receptor, Epidermal Growth Factor/genetics; Receptor, Epidermal Growth Factor/metabolism; Tyrosine/genetics; Tyrosine/metabolism; Ubiquitin-Protein Ligases/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:EGFR_original		GO:0005886: plasma membrane	EXP: Inferred from Experiment: :	C

References

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