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.
Original languageEnglish
JournalJournal of Biological Chemistry
StatePublished - 2009

ID: 356179