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The Stat proteins function both as cytoplasmic signal transducers and as activators of transcription. Seven mammalian Stat proteins have been identified: Stat1-4, Stat5a, 5b, and Stat6. Stat4 has been shown to play an important role in development of T helper cells, specifically the Th1 subset. Stat4 is activated by IL-12 and by type 1 interferons. Knockout mice supported the role that Stat4 plays in IL-12 signaling because lymphocytes from Stat 4-/- mice could not differentiate into Th1 cells or produce IFNγ in response to treatment with IL-12. IFNγ plays an important role in host defense. A key component in the activation of Stat4 is the phosphorylation on tyrosine and serine residues in response to IL-12 stimulation. IL-12 stimulation leads to the phosphorylation of Stat4 on tyrosine 693 and serine 721. Transcriptional activity of Stat4 has been shown to be significantly reduced when residues Y693 and S721 are mutated.Western Blotting
