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

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