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

by Pitcher, Julie A , Etienne‐Manneville, Sandrine , Camand, Emeline , Gibson, Lucien C D , Lima‐Fernandes, Evelyne , Boularan, Cédric , Scott, Mark G H , Achour, Lamia , Benmerah, Alexandre , Baillie, George S , Kotelevets, Larissa , Chastre, Eric , Marullo, Stefano , Enslen, Hervé

in Akt / Animals / Arrestins - antagonists & inhibitors / Arrestins - genetics / Arrestins - metabolism / Arrestins - physiology / beta-Arrestins / cell migration / Cell Movement - drug effects / Cell Movement - genetics / cell proliferation / Cell Proliferation - drug effects / Cells, Cultured / Cercopithecus aethiops / COS Cells / EMBO05 / EMBO37 / Gene Knockdown Techniques / HeLa Cells / Humans / Mice / Protein Binding - drug effects / Protein Binding - genetics / Protein Binding - physiology / PTEN / PTEN Phosphohydrolase - genetics / PTEN Phosphohydrolase - metabolism / PTEN Phosphohydrolase - physiology / RNA, Small Interfering - pharmacology / Signal Transduction - drug effects / Signal Transduction - genetics / Signal Transduction - physiology / β-arrestin

2011

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

2011

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

2011

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Journal Article

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

Pitcher, Julie A,

Etienne‐Manneville, Sandrine,

Camand, Emeline,

Gibson, Lucien C D,

Lima‐Fernandes, Evelyne,

Boularan, Cédric,

Scott, Mark G H,

Achour, Lamia,

Benmerah, Alexandre,

Baillie, George S,

Kotelevets, Larissa,

Chastre, Eric,

Marullo, Stefano,

Enslen, Hervé

2011

Overview

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. This paper discovers β‐arrestins as novel binding partner for PTEN. With functional implications for Rho and AKT signalling, the paper adds new insight into the regulation of PTEN by cell surface receptor signalling pathways.

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Publisher

John Wiley & Sons, Ltd,Nature Publishing Group UK,Nature Publishing Group

Subject

Akt

/ Animals

/ Arrestins - antagonists & inhibitors

/ Arrestins - genetics

/ Arrestins - metabolism

/ Arrestins - physiology

/ beta-Arrestins