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Cited by 6,080Cytokine Signaling Pathways and Interactionsinterferon and immune responsesNF-κB Signaling Pathways

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Jak-STAT Pathways and Transcriptional Activation in Response to IFNs and Other Extracellular Signaling Proteins

Darnell, James E., Kerr, lan M., Stark, George R.·1994·Science
DOI 10.1126/science.8197455
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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.

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Metadata

Authors
Darnell, J. E., Kerr, L. M., & Stark, G. R.
Affiliations
  • Rockefeller University (US)
  • Case Comprehensive Cancer Center (US)
ORCID
Stark, George R.
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
1994-06-03
Volume
264
Issue
5164
Pages
1415-1421
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
DOI
10.1126/science.8197455
OpenAlex
W2029275361
Cited by
6,080
References
85
Citations by year
2026: 84 · 2025: 139 · 2024: 175 · 2023: 170 · 2022: 183 · 2021: 177 · 2020: 162 · 2019: 155 · 2018: 121 · 2017: 166 · 2016: 148 · 2015: 152 · 2014: 160 · 2013: 207 · 2012: 188
FWCI
28.59
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords
JAK/STAT signaling, interferon-alpha, interferon-gamma, signal transduction, STAT proteins, transcriptional activation, JAK kinases, interferon receptor, nuclear translocation, DNA binding
MeSH terms
Amino Acid Sequence, Animals, Base Sequence, Cell Line, DNA-Binding Proteins, Genes, Genetic Complementation Test, Humans, Interferon-gamma, Molecular Sequence Data, Mutation, Protein-Tyrosine Kinases, Regulatory Sequences, Nucleic Acid, Transcription Factors, Signal Transduction, Transcriptional Activation, Interferon-alpha, Interferon-Stimulated Gene Factor 3, Interferon-Stimulated Gene Factor 3, gamma Subunit

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