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Ubiquitination switches EphA2 vesicular traffic from a continuous safeguard to a finite signalling mode

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Listed:
  • Ola Sabet

    (Max Planck Institute of Molecular Physiology)

  • Rabea Stockert

    (Max Planck Institute of Molecular Physiology)

  • Georgia Xouri

    (Max Planck Institute of Molecular Physiology)

  • Yannick Brüggemann

    (Max Planck Institute of Molecular Physiology
    Faculty of Chemistry and Chemical Biology)

  • Angel Stanoev

    (Max Planck Institute of Molecular Physiology)

  • Philippe I. H. Bastiaens

    (Max Planck Institute of Molecular Physiology
    Faculty of Chemistry and Chemical Biology)

Abstract

Autocatalytic phosphorylation of receptor tyrosine kinases (RTKs) enables diverse, context-dependent responses to extracellular signals but comes at the price of autonomous, ligand-independent activation. Using a conformational biosensor that reports on the kinase activity of the cell guidance ephrin receptor type-A (EphA2) in living cells, we observe that autonomous EphA2 activation is suppressed by vesicular recycling and dephosphorylation by protein tyrosine phosphatases 1B (PTP1B) near the pericentriolar recycling endosome. This spatial segregation of catalytically superior PTPs from RTKs at the plasma membrane is essential to preserve ligand responsiveness. Ligand-induced clustering, on the other hand, promotes phosphorylation of a c-Cbl docking site and ubiquitination of the receptor, thereby redirecting it to the late endosome/lysosome. We show that this switch from cyclic to unidirectional receptor trafficking converts a continuous suppressive safeguard mechanism into a transient ligand-responsive signalling mode.

Suggested Citation

  • Ola Sabet & Rabea Stockert & Georgia Xouri & Yannick Brüggemann & Angel Stanoev & Philippe I. H. Bastiaens, 2015. "Ubiquitination switches EphA2 vesicular traffic from a continuous safeguard to a finite signalling mode," Nature Communications, Nature, vol. 6(1), pages 1-13, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9047
    DOI: 10.1038/ncomms9047
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