c-Cbl directs EGF receptors into an endocytic pathway that involves the ubiquitin-interacting motif of Eps15

Journal of Cell Science
Annemieke A de MelkerJannie Borst

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.

References

Sep 1, 1993·Molecular and Cellular Biology·F FazioliP P Di Fiore
Dec 1, 1995·The Journal of Cell Biology·A BenmerahN Cerf-Bensussan
Nov 15, 1996·The Journal of Biological Chemistry·F TebarT Kirchhausen
Feb 24, 1997·The Journal of Cell Biology·S van DelftP M van Bergen en Henegouwen
Apr 18, 1998·The Journal of Cell Biology·A BenmerahN Cerf-Bensussan
Jan 1, 1997·Critical Reviews in Oncogenesis·L Smit, J Borst
Jul 8, 1998·Proceedings of the National Academy of Sciences of the United States of America·S MiyakeH Band
Jul 22, 1998·Molecular and Cellular Biology·M A MurphyD D Bowtell
Jul 10, 1999·Science·M Marsh, H T McMahon
Feb 1, 2000·The Journal of Biological Chemistry·A BenmerahA Dautry-Varsat
Mar 27, 2001·Nature Reviews. Molecular Cell Biology·L Hicke
Oct 19, 2001·Oncogene·A Y TsygankovG Swaminathan
Mar 29, 2002·Nature·Howard Riezman
May 4, 2002·Nature Cell Biology·Camilla RaiborgHarald Stenmark
Jun 20, 2002·The Journal of Biological Chemistry·Elsa KlapiszPaul M P van Bergen en Henegouwen
Aug 3, 2002·Nature Reviews. Molecular Cell Biology·Alexander Sorkin, Mark Von Zastrow
Sep 10, 2002·Proceedings of the National Academy of Sciences of the United States of America·Kaisa HaglundIvan Dikic
Apr 30, 2003·Nature Cell Biology·Kaisa HaglundIvan Dikic
Apr 30, 2003·The Journal of Biological Chemistry·Yaron MosessonYosef Yarden
Jun 5, 2003·Nature Reviews. Molecular Cell Biology·Pier Paolo Di FioreKay Hofmann
Oct 23, 2003·Annual Review of Cell and Developmental Biology·Linda Hicke, Rebecca Dunn
Nov 11, 2003·Trends in Biochemical Sciences·Kaisa HaglundIvan Dikic

❮ Previous
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Citations

Sep 6, 2007·Cancer Metastasis Reviews·Alan G RamsayIan R Hart
Jan 24, 2006·Nature Cell Biology·Daniela HoellerIvan Dikic
Jun 6, 2009·Annual Review of Biochemistry·Zhimin Lu, Tony Hunter
Oct 10, 2009·Cell Communication and Signaling : CCS·Paul Mp van Bergen En Henegouwen
Mar 22, 2006·Proceedings of the National Academy of Sciences of the United States of America·Dong Ping TanDaniel Alkon
Aug 19, 2007·Seminars in Cell & Developmental Biology·Ian G Mills
Aug 23, 2006·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Masaru MitsushimaNoriyuki Kioka
May 29, 2015·Animal : an International Journal of Animal Bioscience·S LervikI Olsaker
Jul 18, 2006·Mechanisms of Development·Li-Mei PaiTrudi Schüpbach
Feb 5, 2011·Cancer Biology & Therapy·Toni M BrandDeric L Wheeler
May 21, 2013·The American Journal of Pathology·Jinhua TangShougang Zhuang
Dec 14, 2018·Cells·Ping Wee, Zhixiang Wang
Jun 3, 2006·Journal of Cellular Physiology·Gayathri Swaminathan, Alexander Y Tsygankov
Apr 18, 2018·Annual Review of Biochemistry·Marcel MettlenSandra L Schmid
Aug 18, 2006·Molecular Pharmacology·Negin P MartinJohn P O'Bryan
Aug 24, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yong-Jiu JinSteven J Burakoff
Apr 24, 2007·The Journal of Biological Chemistry·Ning LiLisa A Elferink
Sep 15, 2005·Journal of Cell Science·Elsa Regan-KlapiszPaul M P van Bergen en Henegouwen

❮ Previous
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