c-Cbl directs EGF receptors into an endocytic pathway that involves the ubiquitin-interacting motif of Eps15
10.1242/jcs.01354
Crossref journal-article
The Company of Biologists
Journal of Cell Science (237)
Abstract

c-Cbl associates with the activated EGF receptor before endocytosis. We here reveal that the capacity of c-Cbl to promote receptor internalization depends on its ubiquitin ligase activity, which functionally connects the EGF receptor to Eps15, a mediator of clathrin-coated pit formation. EGF-induced phosphorylation of Eps15, as well as recruitment of Eps15 to the plasma membrane and its co-localization with the EGF receptor in endosomes required the ubiquitin ligase activity of c-Cbl. This suggested that ubiquitin provides a direct or indirect link between the receptor and Eps15. Indeed, EGF-induced redistribution of Eps15 to the plasma membrane and endosomes depended on its ubiquitin-interacting motif. Upon over-expression, the ubiquitin-interacting motif abrogated the capacity of c-Cbl to promote EGF receptor endocytosis and only allowed receptor internalization via a route that lacked Eps15. Our findings disclose a novel function for the c-Cbl ubiquitin ligase and identify ubiquitin as a module that directs the EGF receptor into an endocytic pathway involving Eps15.

Bibliography

de Melker, A. A., van der Horst, G., & Borst, J. (2004). c-Cbl directs EGF receptors into an endocytic pathway that involves the ubiquitin-interacting motif of Eps15. Journal of Cell Science, 117(21), 5001–5012.

Authors 3
  1. Annemieke A. de Melker (first)
  2. Gerda van der Horst (additional)
  3. Jannie Borst (additional)
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Dates
Type When
Created 20 years, 11 months ago (Sept. 21, 2004, 9:12 p.m.)
Deposited 4 years, 2 months ago (June 25, 2021, 5:17 p.m.)
Indexed 4 months, 4 weeks ago (March 30, 2025, 9:10 p.m.)
Issued 20 years, 10 months ago (Oct. 1, 2004)
Published 20 years, 10 months ago (Oct. 1, 2004)
Published Print 20 years, 10 months ago (Oct. 1, 2004)
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@article{de_Melker_2004, title={c-Cbl directs EGF receptors into an endocytic pathway that involves the ubiquitin-interacting motif of Eps15}, volume={117}, ISSN={0021-9533}, url={http://dx.doi.org/10.1242/jcs.01354}, DOI={10.1242/jcs.01354}, number={21}, journal={Journal of Cell Science}, publisher={The Company of Biologists}, author={de Melker, Annemieke A. and van der Horst, Gerda and Borst, Jannie}, year={2004}, month=oct, pages={5001–5012} }