PI3 kinase isoform p110? is more important than p110? in KIT signaling in hematopoietic cells

PI3 kinases are important for KIT signaling and KIT mutants mediated cell transformation. In order to know the difference of PI3 kinase isoforms p110?? and p110?? in the signaling of wild-type KIT and the often occurred KIT mutation D816V in hematopoietic malignancy mastocytosis, the predominant PI3 kinase isoform p110?? in hematopoietic tissues was knocked out in hematopoietic cells. We found that loss of p110?? expression dramatically inhibits PI3 kinase activation mediated by both wild-type KIT and KIT/D816V. By over expression of p110?? in p110?? knock out cells, wild-type KIT mediated PI3 kinase activation was not changed while over expression of p110?? increased PI3 kinase activation. Similarly, in KIT/D816V expressing cells without p110?? expression, over expression of p110?? but not p110?? restored PI3 kinase activation. In agreement with the signaling results, cell proliferation, cell survival and cell cycle assay further showed that over expression of p110?? but not p110?? in p110?? knock out cells increases both wild-type KIT and KIT/D816V mediated cell survival and proliferation. These results suggested that p110?? plays a more important role than p110?? in KIT signaling and KIT mutant mediated cell transformation in hematopoietic cells.