Tissue-Specific Function of STAT3

The STAT family of transcription factors was first identified in analyses of IFN-mediated signaling pathways (1). Subsequently, several STAT family members were identified, and in vitro studies indicated that individual STAT proteins were phosphorylated on their tyrosine residues in response to distinct cytokines, indicating that the STAT family represents the specificity of cytokines. Indeed, studies with knockout mice clearly established that several STAT family proteins play essential roles in their cytokine-mediated biological functions (2). For instance, Stat1- and Stat2-deficient mice displayed impaired response to IFNs. Stat4 and Stat6 deficiencies resulted in impaired response to IL-12 and IL-4, respectively. Stat5a and Stat5b have been revealed to be important in biological functions mediated by several cytokines, including growth hormone, prolactin, IL-2, and IL-15. All these knockout mice were born normally; however, Stat3 deficiency led to early embryonic lethality. Therefore, in the course of analysis cytokine-mediated function of Stat3 in vivo, a tissue-specific knockout approach was conducted, which revealed the important roles of Stat3 in various tissues in vivo.