Distinct functional outputs of PTEN signalling are controlled by dynamic association with β-arrestins.
Copyright policy )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 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.
- Inserm France
- University of Paris France
- French National Centre for Scientific Research France
- Institut des Sciences Biologiques France
- Institut Cochin France
Arrestins, PTEN Phosphohydrolase, Mice, Cell Movement, Gene Knockdown Techniques, COS Cells, Chlorocebus aethiops, Animals, Humans, RNA, Small Interfering, Cells, Cultured, beta-Arrestins, Cell Proliferation, HeLa Cells, Protein Binding, Signal Transduction
Arrestins, PTEN Phosphohydrolase, Mice, Cell Movement, Gene Knockdown Techniques, COS Cells, Chlorocebus aethiops, Animals, Humans, RNA, Small Interfering, Cells, Cultured, beta-Arrestins, Cell Proliferation, HeLa Cells, Protein Binding, Signal Transduction
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