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

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

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 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
Volume299
Issue number1
DOIs
StatePublished - Sep 10 2004

Fingerprint

1-Phosphatidylinositol 4-Kinase
Cytokines
S Phase
Phosphorylation
Cell Proliferation
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Interleukin-3
G1 Phase
Erythropoietin
Intercellular Signaling Peptides and Proteins
Cell Culture Techniques
Mutation

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Henry, Matthew K. ; Nimbalkar, Dipali ; Hohl, Raymond ; Quelle, Frederick W. / Cytokine-induced phosphoinositide 3-kinase activity promotes Cdk2 activation in factor-dependent hematopoietic cells. In: Experimental Cell Research. 2004 ; Vol. 299, No. 1. pp. 257-266.
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Cytokine-induced phosphoinositide 3-kinase activity promotes Cdk2 activation in factor-dependent hematopoietic cells. / Henry, Matthew K.; Nimbalkar, Dipali; Hohl, Raymond; Quelle, Frederick W.

In: Experimental Cell Research, Vol. 299, No. 1, 10.09.2004, p. 257-266.

Research output: Contribution to journalArticle

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