PI3 kinase isoform p110δ is more important than p110α in KIT signaling in hematopoietic cells

[摘要] PI3 kinases are important for KIT signaling and KIT mutants mediated cell transformation. In order to know thedifference of PI3 kinase isoforms p110α and p110δ in the signaling of wild-type KIT and the often occurred KIT mutationD816V in hematopoietic malignancy mastocytosis, the predominant PI3 kinase isoform p110δ in hematopoietic tissues wasknocked out in hematopoietic cells. We found that loss of p110δ expression dramatically inhibits PI3 kinase activationmediated by both wild-type KIT and KIT/D816V. By over expression of p110α in p110δ knock out cells, wild-type KITmediated PI3 kinase activation was not changed while over expression of p110δ increased PI3 kinase activation.Similarly, in KIT/D816V expressing cells without p110δ expression, over expression of p110δ but not p110α restoredPI3 kinase activation. In agreement with the signaling results, cell proliferation, cell survival and cell cycle assay furthershowed that over expression of p110δ but not p110α in p110δ knock out cells increases both wild-type KIT and KIT/D816V mediated cell survival and proliferation. These results suggested that p110δ plays a more important role thanp110α in KIT signaling and KIT mutant mediated cell transformation in hematopoietic cells.

[学科分类] 仪器

[关键词] Mastocytosis;Mutation;Cell transformation