Polypeptide Signaling to the Nucleus through Tyrosine Phosphorylation of Jak and Stat Proteins

Shual, K., Ziemiecki, A., Wilks, A. F., Harpur, A. G., Sadowski, H. B., Gilman, M. Z., Darnell, J. E. (December 1993) Polypeptide Signaling to the Nucleus through Tyrosine Phosphorylation of Jak and Stat Proteins. Nature, 366 (6455). pp. 580-583. ISSN 0028-0836

URL: http://www.ncbi.nlm.nih.gov/pubmed/7504784
DOI: 10.1038/366580a0

Abstract

BINDING of interferons IFN-alpha and IFN-gamma to their cell surface receptors promptly induces tyrosine phosphorylation of latent cytoplasmic transcriptional activators1-4 (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 pathway5 and for Jak2 (ref. 6), a kinase with similar sequence7, 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 Tyr 701 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.

Item Type: Paper
Uncontrolled Keywords: TRANSCRIPTION FACTOR SH3 DOMAINS IFN-GAMMA INTERFERON BINDING ACTIVATION DEFINE KINASE
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression > phosphorylation
organs, tissues, organelles, cell types and functions > tissues types and functions > signal transduction
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase > tyrosine kinase
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > protein tyrosine phosphatase
CSHL Authors:
Communities: CSHL labs
Depositing User: Matt Covey
Date: 9 December 1993
Date Deposited: 12 Apr 2016 15:09
Last Modified: 12 Apr 2016 15:09
Related URLs:
URI: http://repository.cshl.edu/id/eprint/32575

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