How cells respond to interferons.

  title={How cells respond to interferons.},
  author={George R. Stark and Ian M. Kerr and Bryan R. G. Williams and Robert H. Silverman and Robert D. Schreiber},
  journal={Annual review of biochemistry},
Interferons play key roles in mediating antiviral and antigrowth responses and in modulating immune response. The main signaling pathways are rapid and direct. They involve tyrosine phosphorylation and activation of signal transducers and activators of transcription factors by Janus tyrosine kinases at the cell membrane, followed by release of signal transducers and activators of transcription and their migration to the nucleus, where they induce the expression of the many gene products that… 

Figures from this paper

The PI3' kinase pathway in interferon signaling.

  • S. KaurS. UddinL. Platanias
  • Biology
    Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research
  • 2005
The phosphatidylinositol 3'-kinase (PI3'K) pathway has emerged as one of the critical players in IFN signal transduction and is the focus of this review.

CCAAT/enhancer binding proteins and interferon signaling pathways.

  • D. KalvakolanuS. Roy
  • Biology
    Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research
  • 2005
This work describes one such pathway wherein transcription factor CAAAT/enhancer binding protein-beta (C/EBP-beta) is controlled via IFN-gamma-induced MAPK signaling pathways.

Interleukins and STAT signaling.

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

  • G. Stark
  • Biology
    Cytokine & growth factor reviews
  • 2007

The Jak-Stat Signaling Pathway of Interferons System: Snapshots

A better understanding of the exact mechanism involved in IFNs signaling pathways and the structure-function relationships of the IFNs system components will allow researchers to improve and expand the therapeutic potential of these naturally occurring molecules.

Akt and mRNA translation by interferons

The accumulating evidence on the importance of Akt inIFN-signaling is reviewed, with particular emphasis on its role in mRNA translation of IFN-sensitive genes, and the implications on the overall perception of the Akt pathway are discussed.

The interferon signaling network and transcription factor C/EBP-beta.

The non-STAT pathways that participate in IFN-induced responses are described and the role played by transcription factor C/EBP-beta in mediating these responses is focused on.



Interferon induction of gene expression through the Jak–Stat pathway

Differential activation and combinatorial association of these transcription factors produce the biological responses characteristic of each IFN.

Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins.

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 phosphorylate substrate proteins called STATs (signal transducers and activators of transcription).

Transcriptional responses to polypeptide ligands: the JAK-STAT pathway.

This review will examine how two receptor associated tyrosine kinases from the JAK family mediate the transduction of signal directly from receptor to nucleus.

Cellular responses to interferon-gamma.

Much of the cellular response to IFN-gamma can be described in terms of a set of integrated molecular programs underlying well-defined physiological systems, for example the induction of efficient antigen processing for MHC-mediated antigen presentation, which play clearly defined roles in pathogen resistance.

A family of cytokine-inducible inhibitors of signalling

Transcription of all four SOCS genes is increased rapidly in response to interleukin-6, in vitro and in vivo, suggesting they may act in a classic negative feedback loop to regulate cytokine signal transduction.

Modulation of interferon signaling in human fibroblasts by phorbol esters

Competitive inhibition studies were consistent with the DNA-protein complex at the cap site of ISG54 containing proteins with DNA binding sites in common with those which also interact with the ISRE, suggesting a unique regulatory mechanism by which phorbol esters can modulate IFN signaling.

Regulation of Interferon-γ-Activated STAT1 by the Ubiquitin-Proteasome Pathway

STAT1 proteins activated by interferon-γ treatment in HeLa cells were shown to be stabilized by a proteasome inhibitor and ubiquitinated in vivo, suggesting the amount of activated STAT1 may be negatively regulated by the ubiquitin-proteasome pathway.

Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor.

The interferon-alpha-stimulated gene factor 3 (ISGF3), a transcriptional activator, contains three proteins that reside in the cell cytoplasm until they are activated in response to IFN-alpha, and may link occupation of a specific polypeptide receptor with activation of transcription of a set of specific genes.

Regulation of STAT‐dependent pathways by growth factors and cytokines

How JAK‐STAT pathways transduce signals initiated by both cytokines and growth factors is described, focusing on how specificity is achieved through STAT‐receptor interactions and on how receptor‐associated kinases function in STAT activation.

The role of the dsRNA-activated kinase, PKR, in signal transduction

Phosphorylation of IκB by PKR results in the transcriptional activation of NFκB-dependent genes including interferon beta (IFN-β) and PKR is also implicated as playing a role at either the translational or transcriptional level in the signal transduction pathways of other cytokines including IL3, PDGF and IFN γ.