Interferon-induced nuclear signalling by Jak protein tyrosine kinases
- 1 December 1993
- journal article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 366 (6455), 583-585
- https://doi.org/10.1038/366583a0
Abstract
Interferons IFN-alpha/beta and IFN-gamma act through independent cell-surface receptors, inducing gene expression through tyrosine phosphorylation of cytoplasmic transcription factors . IFN-alpha stimulates phosphorylation and nuclear localization of the 84/91K and 113K subunits of latent ISGF3 (interferon-stimulated gene factor 3), which combine with the 48K DNA-binding subunit to bind regulatory elements of IFN-alpha-responsive genes. IFN-gamma activates p91 alone, inducing IFN-gamma-responsive genes through a distinct DNA element. Genetic complementation studies implicated the tyrosine kinase Tyk2 in IFN-alpha signalling and, more recently, the related Jak2 kinase in IFN-gamma signalling. We now present biochemical evidence for Jak-family kinase involvement in IFN signal transduction. Jak1 was activated in response to IFN-alpha and IFN-gamma; Jak2 responded exclusively to IFN-gamma. Overexpression of either Jak1 or Jak2 stimulated p91 DNA-binding activity and p91-dependent transcription. Overexpression also activated endogenous Jak kinases, suggesting that interactions between Jak kinases are required during interferon signalling.Keywords
This publication has 25 references indexed in Scilit:
- Ras-Independent Growth Factor Signaling by Transcription Factor Tyrosine PhosphorylationScience, 1993
- A Single Phosphotyrosine Residue of Stat91 Required for Gene Activation by Interferon-γScience, 1993
- Two domains of ISGF3 gamma that mediate protein-DNA and protein-protein interactions during transcription factor assembly contribute to DNA-binding specificity.Molecular and Cellular Biology, 1993
- Activation of Transcription by IFN-γ: Tyrosine Phosphorylation of a 91-kD DNA Binding ProteinScience, 1992
- Tyrosine phosphorylation is required for activation of an alpha interferon-stimulated transcription factor.Proceedings of the National Academy of Sciences of the United States of America, 1992
- Interferon-Dependent Tyrosine Phosphorylation of a Latent Cytoplasmic Transcription FactorScience, 1992
- Subunit of an alpha-interferon-responsive transcription factor is related to interferon regulatory factor and Myb families of DNA-binding proteins.Molecular and Cellular Biology, 1992
- Interferon-alpha regulates nuclear translocation and DNA-binding affinity of ISGF3, a multimeric transcriptional activator.Genes & Development, 1990
- Cytoplasmic activation of ISGF3, the positive regulator of interferon-alpha-stimulated transcription, reconstituted in vitro.Genes & Development, 1989
- Rapid activation by interferon alpha of a latent DNA-binding protein present in the cytoplasm of untreated cells.Proceedings of the National Academy of Sciences of the United States of America, 1989