Journal ArticleDOI
Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins
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TLDR
A previously unrecognized direct signal transduction pathway to the nucleus has been uncovered: IFN-receptor interaction at the cell surface leads to the activation of kinases of the Jak family that phosphorylate substrate proteins called STATs (signal transducers and activators of transcription).Abstract:
Through the study of transcriptional activation in response to interferon alpha (IFN-alpha) and interferon gamma (IFN-gamma), a previously unrecognized direct signal transduction pathway to the nucleus has been uncovered: IFN-receptor interaction at the cell surface leads to the activation of kinases of the Jak family that then phosphorylate substrate proteins called STATs (signal transducers and activators of transcription). The phosphorylated STAT proteins move to the nucleus, bind specific DNA elements, and direct transcription. Recognition of the molecules involved in the IFN-alpha and IFN-gamma pathway has led to discoveries that a number of STAT family members exist and that other polypeptide ligands also use the Jak-STAT molecules in signal transduction.read more
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References
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Journal ArticleDOI
A protein tyrosine kinase in the interferon alpha/beta signaling pathway.
TL;DR: The genetic complementation of this mutant and the identification and cloning of the wild-type gene that corrects the defect are described and shows that tyk2 links the interferon alpha/beta receptor to the cytoplasmic transcription factor that mediates activation of interferons-responsive genes.
Journal ArticleDOI
A single phosphotyrosine residue of Stat91 required for gene activation by interferon-gamma
TL;DR: Interferon-gamma stimulates transcription of specific genes by inducing tyrosine phosphorylation of a 91-kilodalton cytoplasmic protein ( STAT for signal transducer and activator of transcription).
Journal ArticleDOI
Activation of transcription by IFN-gamma: tyrosine phosphorylation of a 91-kD DNA binding protein
TL;DR: Through cross-linking and the use of specific antibodies GAF was found to be a 91-kilodalton DNA binding protein that was previously identified as one of four proteins in interferon-stimulated gene factor-3 (ISGF-3), a transcription complex activated by IFN-alpha.
Journal ArticleDOI
The protein tyrosine kinase JAK1 complements defects in interferon-α/β and -γ signal transduction
Mathias Müller,James Briscoe,Carl D. Laxton,Dmitry Guschin,Andrew Ziemiecki,Olli Silvennoinen,Ailsa G. Harpur,Giovanna Barbieri,Bruce A. Witthuhn,Chris Schindler,Sandra Pellegrini,Andrew F. Wilks,James N. Ihle,George R. Stark,lan M. Kerr +14 more
TL;DR: A cell line is produced which lacks the protein tyrosine kinase JAK1 and is completely defective in interferon response, but implementation of this mutant with JAK2 restored the response, establishing the requirement for JAK 1 in both the interferons-& alpha;/&# 38; beta; and -& #38; gamma; signal transduction pathways.
Journal ArticleDOI
A common nuclear signal transduction pathway activated by growth factor and cytokine receptors.
TL;DR: Two unrelated receptors may activate a common nuclear signal transduction pathway that, through differential use of latent cytoplasmic proteins, permits these receptors to regulate both common and unique sets of genes.
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