Transcription factors mediating interleukin-3 survival signals

Interleukin-3 (IL-3) is one of the major hematopoietic cytokines that regulate the survival of hematopoietic cells of various lineages. Although the mechanism underlying the survival effect of IL-3 has been investigated intensively for more than a decade, our knowledge of the survival-signaling network remains incomplete. Binding of IL-3 to its cognate receptors initiates rapid tyrosine phosphorylation of Janus kinases (JAKs) and of signal transducer and activator of transcription (STAT) proteins, as well as activation of the phosphatidylinositol-3 kinase (PI-3K)/Akt and Ras/Raf/MAPK kinase (MEK)/mitogen-activated protein kinase (MAPK) pathways. These signals culminate in induction of a constellation of antiapoptotic genes and prevent cell death from occurring. Thus IL-3 signaling has substantial effects on kinase activation and gene transcription. Previous articles have summarized the roles of these kinase pathways in cell proliferation and survival. In this chapter, we will focus on the role of several newly characterized transcriptional factors, which are targets of these initial kinase cascades and bridge the gap between kinases and survival effector genes, in transducing the IL-3 survival signal. The biological significance of the existence of these multiple survival-specific transcription pathways will also be discussed.