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.
MeSH terms
-
Active Transport, Cell Nucleus / physiology
-
Animals
-
Caenorhabditis elegans / genetics
-
Caenorhabditis elegans / metabolism*
-
Caenorhabditis elegans Proteins
-
Cell Line
-
Cell Nucleus / genetics
-
Cell Nucleus / metabolism*
-
Enzyme Activation / physiology
-
Humans
-
Phosphatidylinositol 3-Kinases / genetics
-
Phosphatidylinositol 3-Kinases / metabolism*
-
Protein Serine-Threonine Kinases
-
Proto-Oncogene Proteins c-akt / genetics
-
Proto-Oncogene Proteins c-akt / metabolism
-
Signal Transduction / physiology*
-
Transcription, Genetic / physiology
-
Wnt Proteins / genetics
-
Wnt Proteins / metabolism*
-
beta Catenin / genetics
-
beta Catenin / metabolism*
Substances
-
Caenorhabditis elegans Proteins
-
Wnt Proteins
-
beta Catenin
-
Protein Serine-Threonine Kinases
-
Proto-Oncogene Proteins c-akt
-
gck-3 protein, C elegans