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Publication Detail
Distinct functional outputs of PTEN signalling are controlled by dynamic association with beta-arrestins
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Article
  • Authors:
    Lima-Fernandes E, Enslen H, Camand E, Kotelevets L, Boularan C, Achour L, Benmerah A, Gibson LCD, Baillie GS, Pitcher JA, Chastre E, Etienne-Manneville S, Marullo S, Scott MGH
  • Publisher:
    NATURE PUBLISHING GROUP
  • Publication date:
    06/07/2011
  • Pagination:
    2557, 2568
  • Journal:
    EMBO J
  • Volume:
    30
  • Issue:
    13
  • Print ISSN:
    0261-4189
  • Language:
    EN
  • Keywords:
    Akt, beta-arrestin, cell migration, cell proliferation, PTEN, PROTEIN-COUPLED RECEPTOR, NUCLEAR EXPORT SIGNAL, TUMOR-SUPPRESSOR PTEN, MEMBRANE ASSOCIATION, PHOSPHATASE-ACTIVITY, PATHWAY, CELL, DOMAIN, PHOSPHORYLATION, BETA-ARRESTIN-1
  • Addresses:
    Scott, MGH
    Inst Cochin
    INSERM
    U1016
    F-75014
    Paris
    France

    CNRS
    UMR8104
    Paris
    France

    Univ Paris 05
    Paris
    France

    Inst Pasteur
    CNRS
    URA 2582
    Paris
    15
    France

    UCL
    Dept Neurosci Physiol & Pharmacol
    London
    England
Abstract
The tumour suppressor PTEN (phosphatase and tensin deleted on chromosome 10) regulates major cellular functions via lipid phosphatase-dependent and -independent mechanisms. Despite its fundamental pathophysiological importance, how PTEN's cellular activity is regulated has only been partially elucidated. We report that the scaffolding proteins beta-arrestins (beta-arrs) are important regulators of PTEN. Downstream of receptor-activated RhoA/ROCK signalling, beta-arrs activate the lipid phosphatase activity of PTEN to negatively regulate Akt and cell proliferation. In contrast, following wound-induced RhoA activation, beta-arrs inhibit the lipid phosphatase-independent anti-migratory effects of PTEN. beta-arrs can thus differentially control distinct functional outputs of PTEN important for cell proliferation and migration. The EMBO Journal (2011) 30, 2557-2568. doi:10.1038/emboj.2011.178; Published online 3 June 2011
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