A Single Phosphotyrosine Residue of Stat91 Required for Gene Activation by Interferon-γ

Interferon-γ (IFN-γ) stimulates transcription of specific genes by inducing tyrosine phosphorylation of a 91-kilodalton cytoplasmic protein (termed STAT for signal transducer and activator of transcription). Stat91 was phosphorylated on a single site (Tyr$^{701}$), and phosphorylation of this site was required for nuclear translocation, DNA binding, and gene activation. Stat84, a differentially spliced product of the same gene that lacks the 38 carboxyl-terminal amino acids of Stat91, did not activate transcription, although it was phosphorylated and translocated to the nucleus and bound DNA. Thus, Stat91 mediates activation of transcription in response to IFN-γ.