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Open Access item H-Ras activation promotes cytoplasmic accumulation and phosphoinositide 3-Oh kinase association of β-Catenin in epidermal keratinocytes

Authors:Espada, Jesús
Pérez-Moreno, Mirna A.
Braga, Vania M. M.
Rodriguez-Viciana, Pablo
Cano, Amparo
Keywords:H-ras, E-cadherin, B -catenin, Adenomatous polyposis coli, Phosphoinositide 3-oh kinase
Issue Date:6-Sep-1999
Publisher:Rockefeller University Press
Citation:Journal of Cell Biology 146(5): 967-980 (1999)
Abstract:The mechanisms underlying downregulation of the cadherin/catenin complexes and β-catenin signaling during tumor progression are not fully understood. We have analyzed the effect of oncogenic H-Ras on E-cadherin/catenin complex formation/stabilization and β-catenin distribution in epidermal keratinocytes. Microinjection or stable expression of V12Ras into keratinocytes promotes the loss of E-cadherin and α-catenin and relocalization of β-catenin to the cytoplasm and nucleus. Moreover, these effects are dependent on PI3K (phosphoinositide 3-OH kinase) activity. Interestingly, a strong association of p85α and p110α subunits of PI3K with β-catenin is induced in V12Ras-expressing keratinocytes, and in vitro binding assays show a direct interaction between β-catenin and p85α. Overexpression of either V12Ras or constitutively active p110α induces metabolic stabilization of β-catenin and promotes its accumulation in cytoplasmic and nuclear pools. In addition, the interaction of β-catenin with the adenomatous polyposis coli protein is blocked in V12Ras and p110α transformants though no changes in glycogen synthase kinase 3 β activity could be detected. Nevertheless, in V12Ras transformants the in vivo phosphorylation of β-catenin in Ser residues is strongly decreased. These results indicate that H-Ras activation induces the relocalization and cytoplasmic stabilization of β-catenin by a mechanism involving its interaction with PI3K.
Description:14 pages, 8 figures.
Publisher version (URL):http://dx.doi.org/10.1083/jcb.146.5.967
Appears in Collections:(IIBM) Artículos

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