Journal article
Cytokine-induced phosphoinositide 3-kinase activity promotes Cdk2 activation in factor-dependent hematopoietic cells
Experimental cell research, Vol.299(1), pp.257-266
2004
DOI: 10.1016/j.yexcr.2004.06.003
PMID: 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.
Details
- Title: Subtitle
- Cytokine-induced phosphoinositide 3-kinase activity promotes Cdk2 activation in factor-dependent hematopoietic cells
- Creators
- Matthew K Henry - Department of Pharmacology, Carver College of Medicine, The University of Iowa, Iowa City, IA, 52242, USADipali Nimbalkar - Department of Pharmacology, Carver College of Medicine, The University of Iowa, Iowa City, IA, 52242, USARaymond J Hohl - Department of Pharmacology, Carver College of Medicine, The University of Iowa, Iowa City, IA, 52242, USAFrederick W Quelle - Department of Pharmacology, Carver College of Medicine, The University of Iowa, Iowa City, IA, 52242, USA
- Resource Type
- Journal article
- Publication Details
- Experimental cell research, Vol.299(1), pp.257-266
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.yexcr.2004.06.003
- PMID
- 15302592
- ISSN
- 0014-4827
- eISSN
- 1090-2422
- Language
- English
- Date published
- 2004
- Academic Unit
- Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040571502771
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