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Phosphatidylinositol 3-kinase (PI3K) 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 (PI3K) signaling does not activate the Wnt cascade. Journal of Biological Chemistry. ISSN 0021-9258.

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Mutational activation of the PI3K pathway occurs in a wide variety of tumors, while activating Wnt pathway mutants are predominantly found in colon cancer. Since 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)-mediated 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 crosstalk between the PI3K and Wnt pathways and that Wnt mediated transcription activity is not modulated by activation of the PI3K/PKB pathway.

Item Type:Article
Institutes:Hubrecht Instituut
ID Code:6992
Deposited On:25 Jan 2010 01:00
Last Modified:13 Oct 2010 12:51

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