The signal transducer and activator of transcription (STAT) proteins are latent cytoplasmic transcription factors that are activated by a variety of cytokines and growth factors to regulate transcription. Upon stimulation, STATs become tyrosine phosphorylated to form functional dimers. Activated STAT dimers then translocate into the nucleus where they directly bind to the promoters of downstream genes to activate transcription. Posttranslational modifications such as phosphorylation and acetylation, the protein inhibitor of activate STAT (PIAS) proteins, and several protein tyrosine phosphatases (PTPases) have been shown to regulate the activity of STATs. This article reviews the current understanding of the functional domains, the regulation, and the physiological roles of STATs in cytokine signaling.

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