Stat (Signal transducer and activators of transcription) proteins mediate the biological activity of cytokines, including interleukins, interferons, erythropoietin, and growth factors
Ligand-receptor interaction activates constitutively-associated JAK family kinases as well as subsequent recruitment and 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, the primary transcription activator induced by interferon binding 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 translocates to the nucleus
This forms an active complex that includes the DNA-binding p48 subunit, and is responsible for modulating interferon-stimulated genes (ISGs) transciption
The 4a monoclonal antibody recognizes the phosphorylated Y701 in Stat1α and Stat1β.