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Review
. 2007 Oct-Dec;18(5-6):419-23.
doi: 10.1016/j.cytogfr.2007.06.013. Epub 2007 Aug 1.

How cells respond to interferons revisited: from early history to current complexity

George R Stark  1
Affiliations
Review

How cells respond to interferons revisited: from early history to current complexity

George R Stark. Cytokine Growth Factor Rev. 2007 Oct-Dec.

Abstract

A brief account of how I became involved in interferon research is followed by recollections of key experiments that led to the discovery of the roles of the JAKs and STATs in interferon-dependent signaling. I then outline the complex responses of cells to interferons, including the roles of kinases other than JAKs and transcription factors other than STATs, differential responses to interferons alpha and beta, modulation of response by prior exposure to other cytokines ("priming"), cytokine-dependent induction of high level expression of STATs 1 and 3 and the activation of a new set of genes by these unphosphorylated STATs, and diverse patterns of STAT activation in different cell types in response to a single interferon.

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Figures

Figure
Figure
Complexity of responses to interferons. In addition to the activation of JAKs and STATs, interferons activate other kinases and transcription factors (TFs), as indicated in detail in the figure. The patterns of STAT, TF and kinase activation in response to each specific interferon are likely to vary substantially among different cell types. Some genes respond only to activated STATs, some only to activated TFs and some only to both together. Examples are given in the figure. For more details, see the reviews [17, 18].
See this image and copyright information in PMC

References

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    1. Friedman RL, Manly SP, McMahon M, Kerr IM, Stark GR. Transcriptional and posttranscriptional regulation of interferon-induced gene expression in human cells. Cell. 1984;38:745–755. - PubMed
    1. Friedman RL, Stark GR. Alpha-interferon-induced transcription of HLA and metallothionein genes containing homologous upstream sequences. Nature. 1985;314:637–639. - PubMed
    1. Dale TC, Rosen JM, Guille MJ, et al. Overlapping sites for constitutive and induced DNA binding factors involved in interferon-stimulated transcription. EMBO J. 1989;8:831–839. - PMC - PubMed
    1. Dale TC, Imam AM, Kerr IM, Stark GR. Rapid activation by interferon alpha of a latent DNA-binding protein present in the cytoplasm of untreated cells. Proc Natl Acad Sci U S A. 1989;86:1203–1207. - PMC - PubMed

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