Here's a 1993 Nature paper with some of the molecular details:
Nature 1993 Dec 9;366(6455):580-583
Polypeptide signalling to the nucleus through tyrosine phosphorylation of
Jak and Stat proteins.
Shual K, Ziemiecki A, Wilks AF, Harpur AG, Sadowski HB, Gilman MZ, Darnell JE
Laboratory of Molecular Cell Biology, Rockefeller University, New York 10021-6399.
Binding of interferons IFN-alpha and IFN-gamma to their cell surface receptors promptly induces tyrosine phosphorylation of
latent cytoplasmic transcriptional activators (or Stat proteins, for signal transducers and activators of transcription).
Interferon-alpha activates both Stat91 (M(r) 91,000; ref. 1) and Stat113 (M(r) 113,000; ref. 2) whereas IFN-gamma
activates only Stat91 (refs 3, 4). The activated proteins then move into the nucleus and directly activate genes induced by
IFN-alpha and IFN-gamma. Somatic cell genetics experiments have demonstrated a requirement for tyrosine kinase-2 (Tyk2)
in the IFN-alpha response pathway and for Jak2 (ref. 6), a kinase with similar sequence, in the IFN-gamma response
pathway. Here we investigate the tyrosine phosphorylation events on Stat and Jak proteins after treatment of cells with IFNs
alpha and gamma and with epidermal growth factor (EGF). Stat91 is phosphorylated on Tyr701 after cells are treated with
IFN-alpha and EGF, as it was after treatment with IFN-gamma (ref. 8). We find that Jak1 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
different kinase. Jak1 may therefore be the enzyme that phosphorylates Tyr 701 in Stat91.
PMID: 7504784, UI: 94077183 |
