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.