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PMID: 22520844 Published · ppublish English Journal Article Review

The JAK-STAT pathway at twenty.

Immunity ·Vol. 36 ·No. 4 ·2012-04-20 ·Pages 503-14

Stark GR, Darnell JE

Abstract

We look back on the discoveries that the tyrosine kinases TYK2 and JAK1 and the transcription factors STAT1, STAT2, and IRF9 are required for the cellular response to type I interferons. This initial description of the JAK-STAT pathway led quickly to additional discoveries that type II interferons and many other cytokines signal through similar mechanisms. This well-understood pathway now serves as a paradigm showing how information from protein-protein contacts at the cell surface can be conveyed directly to genes in the nucleus. We also review recent work on the STAT proteins showing the importance of several different posttranslational modifications, including serine phosphorylation, acetylation, methylation, and sumoylation. These remarkably proficient proteins also provide noncanonical functions in transcriptional regulation and they also function in mitochondrial respiration and chromatin organization in ways that may not involve transcription at all.

MeSH Terms
Animals Chromatin/physiology Humans Interferon Regulatory Factors/metabolism Interferon Type I/metabolism Janus Kinases/metabolism Mitochondria/metabolism Protein Processing, Post-Translational STAT Transcription Factors/metabolism Signal Transduction Transcription, Genetic
Chemicals
Chromatin Interferon Regulatory Factors Interferon Type I STAT Transcription Factors Janus Kinases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Stark George R
Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA. [email protected]
Darnell James E
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2012.03.013
Email
[email protected]
Published
2012-04-20
Pages
503-14
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC3909993
Subset
IM
Grants
NCI NIH HHS · R01 CA095851-08 · United States
NCI NIH HHS · R01 CA095851-07 · United States
NCI NIH HHS · R01 CA095851-06 · United States
NCI NIH HHS · R01 CA095851 · United States
NCI NIH HHS · R01 CA095851-09 · United States
External Links
PubMed source DOI: 10.1016/j.immuni.2012.03.013 PMC Full Text View journal details
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