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

Matthew K. Henry, Dipali Nimbalkar, Raymond J. Hohl, Frederick W. Quelle

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


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 p27Kip1 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.

Original languageEnglish (US)
Pages (from-to)257-266
Number of pages10
JournalExperimental Cell Research
Issue number1
StatePublished - Sep 10 2004

All Science Journal Classification (ASJC) codes

  • Cell Biology


Dive into the research topics of 'Cytokine-induced phosphoinositide 3-kinase activity promotes Cdk2 activation in factor-dependent hematopoietic cells'. Together they form a unique fingerprint.

Cite this