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.