Phosphatidylinositol 3-kinase (PI3K) signaling does not activate the Wnt cascade

S.S. Ng; T. Mahmoudi; E.M. Danenberg; I. Bejaoui; W.B.M. de Lau; H.C. Korswagen; M. Schutte; H. Clevers

doi:10.1074/jbc.M109.078261

Phosphatidylinositol 3-kinase (PI3K) signaling does not activate the Wnt cascade

S.S. Ng, T. Mahmoudi, E.M. Danenberg, I. Bejaoui, W.B.M. de Lau, H.C. Korswagen, M. Schutte, H. Clevers

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

122 Citations (Scopus)

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.

Original language	English
Pages (from-to)	35308-35313
Journal	Journal of Biological Chemistry
Volume	284
Issue number	51
DOIs	https://doi.org/10.1074/jbc.M109.078261
Publication status	Published - 2009

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title = "Phosphatidylinositol 3-kinase (PI3K) signaling does not activate the Wnt cascade",

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.",

author = "S.S. Ng and T. Mahmoudi and E.M. Danenberg and I. Bejaoui and {de Lau}, W.B.M. and H.C. Korswagen and M. Schutte and H. Clevers",

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doi = "10.1074/jbc.M109.078261",

language = "English",

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T1 - Phosphatidylinositol 3-kinase (PI3K) signaling does not activate the Wnt cascade

AU - Ng, S.S.

AU - Mahmoudi, T.

AU - Danenberg, E.M.

AU - Bejaoui, I.

AU - de Lau, W.B.M.

AU - Korswagen, H.C.

AU - Schutte, M.

AU - Clevers, H.

N1 - Reporting year: 2009

PY - 2009

Y1 - 2009

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 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.

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 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.

U2 - 10.1074/jbc.M109.078261

DO - 10.1074/jbc.M109.078261

M3 - Article

SN - 0021-9258

VL - 284

SP - 35308

EP - 35313

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 51

ER -

Phosphatidylinositol 3-kinase (PI3K) signaling does not activate the Wnt cascade

Abstract

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