Abstract
The activation of STAT proteins by cytokines IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21, all of which share the common cytokine receptor γ chain (γc), is one of the earliest signaling events that rapidly transduces signals by these cytokines from membrane to the nucleus. Together with other transcription factors and co-factors, the STAT proteins activated determine cytokine-specific gene expression profiles. In normal human T lymphocytes, the genes that are regulated by IL-2, IL-7, and IL-15, which all activate Stat5, are very similar but differ from the genes regulated by IL-4, which primarily activates Stat6. STAT proteins regulate the expression of cytokine target genes by binding to GAS motifs. Cooperative binding of Stat5 tetramers is crucial in regulating transcription of certain cytokine target genes. For example, IL-2-induced IL-2Rα transcription is regulated by two spatially separated positive regulatory regions and each of which binds Stat5 tetramers as well as other essential transcription factors. Stat5 proteins play vital roles in lymphoid development and function, and for example, these proteins critically regulate NK cell development and function and CD8+ memory T cells homeostasis in vivo. Furthermore, development of lymphoma in Stat5 transgenic mice demonstrates that dysregulated expression of Stat5 proteins, even without detectable constitutive activation, can predispose to malignant transformation in mice. In this chapter, we will describe how Stat5 proteins regulate their target genes in response to γc family cytokines, the roles of Stat5 in T-cell development and function, and the potential role of Stat5 in oncogenesis.
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Lin, JX., Leonard, W.J. (2003). Mechanisms and Biological Consequences of STAT Signaling by Cytokines that Share the Common Cytokine Receptor γ Chain, γc . In: Sehgal, P.B., Levy, D.E., Hirano, T. (eds) Signal Transducers and Activators of Transcription (STATs). Springer, Dordrecht. https://doi.org/10.1007/978-94-017-3000-6_29
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