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EMBO J. 2011 Jun 3;30(13):2557-68. doi: 10.1038/emboj.2011.178.

Distinct functional outputs of PTEN signalling are controlled by dynamic association with β-arrestins.

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1
INSERM, U1016, Institut Cochin, Paris, France.

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 β-arrestins (β-arrs) are important regulators of PTEN. Downstream of receptor-activated RhoA/ROCK signalling, β-arrs activate the lipid phosphatase activity of PTEN to negatively regulate Akt and cell proliferation. In contrast, following wound-induced RhoA activation, β-arrs inhibit the lipid phosphatase-independent anti-migratory effects of PTEN. β-arrs can thus differentially control distinct functional outputs of PTEN important for cell proliferation and migration.

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PMID:
21642958
PMCID:
PMC3155309
DOI:
10.1038/emboj.2011.178
[Indexed for MEDLINE]
Free PMC Article

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