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Phosphatidylinositol 3-kinase signaling does not activate the wnt cascade.

Ng, S.S. and Mahmoudi, T. and Danenberg, E.M. and Bejaoui, I. and Lau de, W.B.M. and Korswagen, H.C. and Schutte, M. and Clevers, H. (2009) Phosphatidylinositol 3-kinase signaling does not activate the wnt cascade. Journal of Biological Chemistry, 284, 35308-13. ISSN 0021-9258.

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Abstract

Mutational activation of the phosphatidylinositol 3-kinase (PI3K) pathway occurs in a wide variety of tumors, whereas activating Wnt pathway mutants are predominantly found in colon cancer. Because GSK3 is a key component of both pathways, it is widely assumed that active PI3K signaling feeds positively into the Wnt pathway by protein kinase B (PKB)-mediatefd inhibition of GSK3. In addition, PKB has been proposed to modulate the canonical Wnt signaling through direct stabilization and nuclear localization of beta-catenin. Here, we show that compartmentalization by Axin of GSK3 prohibits cross-talk between the PI3K and Wnt pathways and that Wnt-mediated transcriptional activity is not modulated by activation of the PI3K/PKB pathway.

Item Type:Article
Institutes:Hubrecht Instituut
ID Code:6952
Deposited On:24 Dec 2009 01:00
Last Modified:13 Oct 2010 12:51

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