| Steroid-like signalling by interferons: making sense of specific gene activation by cytokines. | |
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MedLine Citation:
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PMID: 22452815 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Many cytokines, hormones and growth factors use the JAK (Janus kinase)/STAT (signal transducer and activator of transcription) pathway for cell signalling and specific gene activation. In the classical model, ligand is said to interact solely with the receptor extracellular domain, which triggers JAK activation of STATs at the receptor cytoplasmic domain. Activated STATs are then said to carry out nuclear events of specific gene activation. Given the limited number of STATs (seven) and the activation of the same STATs by cytokines with different functions, the mechanism of the specificity of their signalling is not obvious. Focusing on IFNγ (interferon γ), we have shown that ligand, receptor and activated JAKs are involved in nuclear events that are associated with specific gene activation, where the receptor subunit IFNGR1 (IFNγ receptor 1) functions as a transcription/co-transcription factor and the JAKs are involved in key epigenetic events. RTKs (receptor tyrosine kinases) such as EGFR [EGF (epidermal growth factor) receptor] and FGFR [FGF (fibroblast growth factor) receptor] also undergo nuclear translocation in association with their respective ligands. EGFR and FGFR, like IFNGR1, have been shown to function as transcription/co-transcription factors. The RTKs also regulate other kinases that have epigenetic effects. Our IFNγ model, as well as the RTKs EGFR and FGFR, have similarities to that of steroid receptor signalling. These systems consist of ligand-receptor-co-activator complexes at the genes that they activate. The co-activators consist of transcription factors and kinases, of which the latter play an important role in the associated epigenetics. It is our view that signalling by cytokines such as IFNγ is but a variation of specific gene activation by steroid hormones. |
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Authors:
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Howard M Johnson; Ezra N Noon-Song; Kaisa Kemppainen; Chulbul M Ahmed |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Review |
Journal Detail:
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Title: The Biochemical journal Volume: 443 ISSN: 1470-8728 ISO Abbreviation: Biochem. J. Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-03-28 Completed Date: 2012-05-14 Revised Date: 2013-04-17 |
Medline Journal Info:
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Nlm Unique ID: 2984726R Medline TA: Biochem J Country: England |
Other Details:
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Languages: eng Pagination: 329-38 Citation Subset: IM |
Affiliation:
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Department of Microbiology and Cell Science, University of Florida, Gainesville, FL 32611-0700, USA. johnsnoh@ufl.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Fibroblast Growth Factors / metabolism Gene Expression Regulation* Humans Interferons / metabolism* Signal Transduction* Steroids / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01 056152//PHS HHS; R01 AI056152/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Steroids; 62031-54-3/Fibroblast Growth Factors; 9008-11-1/Interferons |
| Comments/Corrections | |
Erratum In:
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Biochem J. 2012 Jul 15;445(2):295 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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