Journal
EMBO JOURNAL
Volume 30, Issue 13, Pages 2557-2568Publisher
WILEY
DOI: 10.1038/emboj.2011.178
Keywords
Akt; beta-arrestin; cell migration; cell proliferation; PTEN
Categories
Funding
- Association pour la Recherche sur le Cancer [ARC 4954, ARC 3918]
- Agence Nationale pour la Recherche ['ANR' BLAN07-3-187842, 'ANR' BLAN07-1-191659]
- Ligue Contre le Cancer
- Royal Society
- CNRS
- INSERM
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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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