Wnt/β-catenin Pathway Modulates the Sensitivity of the Mutant FLT3 Receptor Kinase Inhibitors in a GSK-3β Dependent Manner.

ABSTRACT: The FLT3 tyrosine kinase receptor is involved in both hematopoiesis and hematological malignancies. The Wnt/β-catenin pathway has been shown to participate in the self-renewal of hematopoietic stem cells and to cooperate with the mutant FLT3 receptors in leukemic transformation. However, the detailed biological impact of such a constitutively activated Wnt pathway remains to be further explored. Here, the authors report that activating mutations of FLT3 constitutively activate β-catenin by inhibition of GSK-3β in a PI3 kinase pathway-dependent manner. Ectopic expression of a dominant negative form of GSK-3β in FLT3-ITD-expressing cells activated β-catenin and blocked the downregulation of the TCF/β-catenin transcriptional activity induced by inhibition of FLT3 kinase. Furthermore, inhibiti

SUBMITTER: Jiang J 

PROVIDER: S-EPMC3092187 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature