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The Eps8 protein coordinates EGF receptor signalling through Rac and trafficking through Rab5

Author

Listed:
  • Letizia Lanzetti

    (Department of Experimental Oncology European Institute of Oncology)

  • Vladimir Rybin

    (Max Planck Institute for Molecular Cell Biology and Genetics, 01307 Dresden, c/o European Molecular Biology Laboratory (EMBL))

  • Maria Grazia Malabarba

    (Department of Experimental Oncology European Institute of Oncology)

  • Savvas Christoforidis

    (Max Planck Institute for Molecular Cell Biology and Genetics, 01307 Dresden, c/o European Molecular Biology Laboratory (EMBL)
    Medical School University of Ioannina)

  • Giorgio Scita

    (Department of Experimental Oncology European Institute of Oncology)

  • Marino Zerial

    (Max Planck Institute for Molecular Cell Biology and Genetics, 01307 Dresden, c/o European Molecular Biology Laboratory (EMBL))

  • Pier Paolo Di Fiore

    (Department of Experimental Oncology European Institute of Oncology
    IFOM, The FIRC Institute for Molecular Oncology)

Abstract

How epidermal growth factor receptor (EGFR) signalling is linked to EGFR trafficking is largely unknown. Signalling and trafficking involve small GTPases of the Rho and Rab families, respectively. But it remains unknown whether the signalling relying on these two classes of GTPases is integrated, and, if it is, what molecular machinery is involved. Here we report that the protein Eps8 connects these signalling pathways. Eps8 is a substrate of the EGFR1, which is held in a complex with Sos1 by the adaptor protein E3b1 (ref. 2), thereby mediating activation of Rac2. Through its src homology-3 domain, Eps8 interacts with RN-tre3. We show that RN-tre is a Rab5 GTPase-activating protein, whose activity is regulated by the EGFR. By entering in a complex with Eps8, RN-tre acts on Rab5 and inhibits internalization of the EGFR. Furthermore, RN-tre diverts Eps8 from its Rac-activating function, resulting in the attenuation of Rac signalling. Thus, depending on its state of association with E3b1 or RN-tre, Eps8 participates in both EGFR signalling through Rac, and trafficking through Rab5.

Suggested Citation

  • Letizia Lanzetti & Vladimir Rybin & Maria Grazia Malabarba & Savvas Christoforidis & Giorgio Scita & Marino Zerial & Pier Paolo Di Fiore, 2000. "The Eps8 protein coordinates EGF receptor signalling through Rac and trafficking through Rab5," Nature, Nature, vol. 408(6810), pages 374-377, November.
    • Handle: RePEc:nat:nature:v:408:y:2000:i:6810:d:10.1038_35042605
    DOI: 10.1038/35042605
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    Cited by:

    1. Oliver M Crook & Aikaterini Geladaki & Daniel J H Nightingale & Owen L Vennard & Kathryn S Lilley & Laurent Gatto & Paul D W Kirk, 2020. "A semi-supervised Bayesian approach for simultaneous protein sub-cellular localisation assignment and novelty detection," PLOS Computational Biology, Public Library of Science, vol. 16(11), pages 1-21, November.

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