TY - JOUR
T1 - Phosphatidylinositol 3-kinase signaling does not activate the Wnt cascade
AU - Ng, Ser Sue
AU - Mahmoudi, Tokameh
AU - Danenberg, Esther
AU - Bejaoui, Inés
AU - de Lau, Wim
AU - Korswagen, Hendrik C.
AU - Schutte, Mieke
AU - Clevers, Hans
PY - 2009/12/18
Y1 - 2009/12/18
N2 - 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 β-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.
AB - 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 β-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.
UR - http://www.scopus.com/inward/record.url?scp=72149109797&partnerID=8YFLogxK
U2 - 10.1074/jbc.M109.078261
DO - 10.1074/jbc.M109.078261
M3 - Article
C2 - 19850932
AN - SCOPUS:72149109797
SN - 0021-9258
VL - 284
SP - 35308
EP - 35313
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 51
ER -