Signal transducer and activator of transcription 4 (STAT4) is a transcription factor belonging to the STAT protein family. It is required for the development of Th1 cells from naive CD4+ T cells and IFN-γ production in response to IL-12. Distribution of STAT4 is restricted to myeloid cells, thymus and testis. In resting human T cells it is expressed at very low levels, but its production is amplified by PHA stimulation. Stat4 is phosphorylated by these tyrosine kinases, homodimerizes via its SH2 domain and translocates into nucleus to activate gene transcription. STAT4 binds to hundreds of sites in the genome, among others to the promoters of genes for cytokines (IFN-γ, TNF), receptors (IL18R1, IL12rβ2, IL18RAP), and signaling factors (MYD88).
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