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

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; r...

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Bibliographic Details
Published in:Nature (London) 1993-12, Vol.366 (6455), p.580-583
Main Authors: Shuai, Ke, Ziemiecki, Andrew, Wilks, Andrew F, Harpur, Ailsa G, Sadowski, Henry B, Gilman, Michael Z, Darnell, James E
Format: Article
Language:English
Subjects:
Amino Acid Sequence
B-Lymphocytes - drug effects
B-Lymphocytes - metabolism
Base Sequence
Binding Sites
Biological and medical sciences
Cell Line
Cell physiology
Cellular biology
Epidermal Growth Factor - pharmacology
Fundamental and applied biological sciences. Psychology
Glutathione Transferase - metabolism
Humans
Interferon-alpha - pharmacology
Interferon-gamma - pharmacology
Janus Kinase 1
Janus Kinase 2
Molecular and cellular biology
Molecular Sequence Data
Phosphorylation
Phosphotyrosine
Protein-Tyrosine Kinases - metabolism
Proteins
Proto-Oncogene Proteins
Recombinant Fusion Proteins - metabolism
Signal transduction
Trans-Activators - metabolism
Tumor Cells, Cultured
Tyrosine - analogs & derivatives
Tyrosine - analysis
Tyrosine - metabolism
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Summary: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.
ISSN:0028-0836
1476-4687
DOI:10.1038/366580a0