Phosphatidylinositol 3-kinase signaling does not activate the Wnt cascade

Ser Sue Ng, Tokameh Mahmoudi, Esther Danenberg, Inés Bejaoui, Wim de Lau, Hendrik C. Korswagen, Mieke Schutte, Hans Clevers

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

123 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)35308-35313
Aantal pagina's6
TijdschriftJournal of Biological Chemistry
Volume284
Nummer van het tijdschrift51
DOI's
StatusGepubliceerd - 18 dec. 2009
Extern gepubliceerdJa

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