Cytokine-induced phosphoinositide 3-kinase activity promotes Cdk2 activation in factor-dependent hematopoietic cells

被引:14
作者
Henry, MK
Nimbalkar, D
Hohl, RJ
Quelle, FW
机构
[1] Univ Iowa, Carver Coll Med, Dept Pharmacol, Iowa City, IA 52242 USA
[2] Univ Iowa, Carver Coll Med, Dept Internal Med, Iowa City, IA 52242 USA
[3] Univ Iowa, Carver Coll Med, Grad Program Immunol, Iowa City, IA 52242 USA
关键词
erythropoietin; interleukin-3; phosphoinositide; 3-kinase; CDK2; proliferation;
D O I
10.1016/j.yexcr.2004.06.003
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 p27K'p, 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. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:257 / 266
页数:10
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