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Title: Cytokine-induced phosphoinositide 3-kinase activity promotes Cdk2 activation in factor-dependent hematopoietic cells. Author: Henry MK, Nimbalkar D, Hohl RJ, Quelle FW. Journal: Exp Cell Res; 2004 Sep 10; 299(1):257-66. PubMed ID: 15302592. Abstract: Cytokine growth factors regulate the proliferation of hematopoietic cells through activation of several distinct signaling pathways. We have assessed the contribution of phosphoinositide 3-kinase (PI3K) pathways to erythropoietin (Epo) and interleukin (IL)-3-induced proliferation of factor-dependent hematopoietic cells. Lack of cytokine-induced PI3K activation caused by receptor mutation or treatment with a specific inhibitor (LY294002) did not prevent proliferation but resulted in an increase in the G1 phase content and doubling time of cell cultures. The reduced proliferation of cells lacking cytokine-induced PI3K activity could be partially restored by overexpressing constitutively active Akt. Inhibition of PI3K activity decreased the proportion of cytokine-treated cells entering S phase and was associated with a significant reduction in cytokine-induced phosphorylation and activation of Cdk2. By contrast, Cdk4 activity and p27(Kip1) expression were not significantly altered by inhibition of PI3K. Together, these observations identify a mechanism through which cytokine-activated PI3K contributes to G1 to S phase progression in factor-dependent hematopoietic cells by enhancing the phosphorylation and activation of Cdk2.[Abstract] [Full Text] [Related] [New Search]