Regulation of survival pathways by IL-3 and induction of apoptosis following IL-3 withdrawal.
The production of hematopoietic cells is regulated by the availability of key cytokines such as interleukin-3 (IL-3). IL-3 promotes the survival and proliferation of bone marrow-derived hematopoietic cells. Recent studies using IL-3-dependent cell lines have begun to shed light on the regulation of apoptosis in cytokine-dependent cells. These studies indicate that IL-3 inhibits apoptosis by stimulating the activation of cellular kinases, including phophatidylinositol (PI) 3-kinase and Akt kinase. On the other hand, withdrawal of IL-3 leads to the activation of caspase proteases and a commitment to cell death. This review will discuss the current state of knowledge regarding the molecular mechanisms of: a) suppression of apoptosis by IL-3, and b) activation of apoptosis following IL-3 withdrawal.
Johnson
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Department of Medicine, University of Pittsburgh, and the University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213-2582, USA. johnsond+@pitt.edu
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007377:Interleukin-3 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D007377:Interleukin-3