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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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.
|Deposited On:||24 Dec 2009 01:00|
|Last Modified:||13 Oct 2010 12:51|
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