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Title

Direct metabolic regulation of β-catenin activity by the p85α regulatory subunit of phosphoinositide 3-OH kinase

AuthorsEspada, Jesús ; Peinado, Héctor; Esteller, Manel; Cano, Amparo
Issue Date2005
PublisherElsevier
CitationExperimental Cell Research 305(2): 409-417 (2005)
AbstractClass IA phosphoinositide 3-OH kinases (PI3K) are lipid kinases composed of catalytic and regulatory subunits. These lipid kinases can regulate the metabolic stability and signaling activity of β-catenin, a central component of the E-cadherin/catenin cell-cell adhesion complex, and of the Wnt signaling pathway. This regulation occurs at the level of glycogen synthase kinase 3 (GSK3), a serine/threonine kinase that marks β-catenin to enter a destruction pathway. In addition, the regulatory subunit p85α directly binds β-catenin, but the role of this interaction in the context of the lipid kinase regulation of β-catenin signaling is unknown. Here we report that expression of exogenous p85α in mouse keratinocytes increases the metabolic stability and has a strong synergistic effect on the transcriptional activity of β-catenin. Both effects are associated to the formation of β-catenin/p85α and inhibition of β-catenin/APC complexes and are independent of GSK3 and PI3K activities. These findings suggest that p85α can act as a direct metabolic regulator of β-catenin activity. © 2005 Elsevier Inc. All rights reserved.
URIhttp://hdl.handle.net/10261/81159
DOI10.1016/j.yexcr.2005.01.009
Identifiersdoi: 10.1016/j.yexcr.2005.01.009
issn: 0014-4827
e-issn: 1090-2422
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