title: Distinct functional outputs of PTEN signalling are controlled by dynamic association with β-arrestins.
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.
authors.affiliation: INSERM, U1016, Institut Cochin, Paris, France.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Lima-Fernandes
authors.forename: Hervé
authors.initials: H
authors.lastname: Enslen
authors.forename: Emeline
authors.initials: E
authors.lastname: Camand
authors.forename: Larissa
authors.initials: L
authors.lastname: Kotelevets
authors.forename: Cédric
authors.initials: C
authors.lastname: Boularan
authors.forename: Lamia
authors.initials: L
authors.lastname: Achour
authors.forename: Alexandre
authors.initials: A
authors.lastname: Benmerah
authors.forename: Lucien C D
authors.initials: LC
authors.lastname: Gibson
authors.forename: George S
authors.initials: GS
authors.lastname: Baillie
authors.forename: Julie A
authors.initials: JA
authors.lastname: Pitcher
authors.forename: Eric
authors.initials: E
authors.lastname: Chastre
authors.forename: Sandrine
authors.initials: S
authors.lastname: Etienne-Manneville
authors.forename: Stefano
authors.initials: S
authors.lastname: Marullo
authors.forename: Mark G H
authors.initials: MG
authors.lastname: Scott
mesh_terms: D000818:Animals; D019390:Arrestins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D019556:COS Cells; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D034741:RNA, Small Interfering; D000071557:beta-Arrestins; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human