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Stat (Signal transducer and activators of transcription) proteins are critical mediators of the biologic activity of cytokines, including interleukins, interferons, erythropoietin, and growth factors. Ligand-receptor interaction leads to activation of constitutively associated JAK family kinases and subsequent recruitment/activation of Stat proteins by tyrosine phosphorylation. Active Stat proteins then move to the nucleus to promote transcription of cytokine-inducible genes. Seven Stat proteins have been cloned, each of which is differentially expressed and/or activated in a cytokine-specific and cell type-specific manner. Stat1 and Stat2 are components of the ISGF3 (Interferon-Stimulated Gene Factor 3) complex, which is the primary transcription activator induced by the binding of the interferon to a specific cell-surface receptor. Stat1 has two alternatively spliced isoforms, 91-kDa Stat1α and 84-kDa Stat1β; Stat1α has 38 additional C-terminal amino acids. In response to the binding of IFNα, IFNγ, EGF, PDGF, or CSF-1 to their respective receptors, the Stat1 subunits become tyrosine phosphorylated at Y701, and the complex is translocated to the nucleus. This results in the formation of an active complex that includes the DNA-binding p48 subunit. This complex is responsible for modulating the transcription of the interferon-stimulated genes (ISGs).Flow Cytometry, Immunofluorescence, Immunoprecipitation, Intracellular Staining, Western Blotting
