Polypeptide signalling to the nucleus through tyrosine phosphorylation of Jak and Stat proteins

BINDING of interferons IFN-α and IFN-γ to their cell surface receptors promptly induces tyrosine phosphorylation of latent cytoplasmic transcriptional activators 1–4 (or Stat proteins, for signal transducers and activators of transcription). Interferon-α activates both Stat91 ( M r 91,000; ref. 1) and Statll3 ( M r 113,000; ref. 2) whereas IFN-γ activates only Stat91 (refs 3, 4). The activated proteins then move into the nucleus and directly activate genes induced by IFN-α and IFN-γ. Somatic cell genetics experiments have demonstrated a requirement for tyrosine kinase-2 (Tyk2) in the IFN-α response pathway 5 and for Jak2 (ref. 6), a kinase with similar sequence 7 , in the IFN-γ response pathway. Here we investigate the tyrosine phosphorylation events on Stat and Jak proteins after treatment of cells with IFNs α and γ and with epidermal growth factor (EGF). Stat91 is phosphorylated on Tyr 701 after cells are treated with IFN-α and EGF, as it was after treatment with IFN-γ (ref. 8). We find that Jakl also becomes phosphorylated on tyrosine after cells are treated with these same three ligands, although each ligand is shown to activate at least one other differ-ent kinase. Jakl may therefore be the enzyme that phosphorylates Tyr701inStat91.