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

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TLDR
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).
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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Erythropoietin induces activation of Stat5 through association with specific tyrosines on the receptor that are not required for a mitogenic response.

TL;DR: The studies presented here demonstrate that this region is also necessary and sufficient for the activation of Stat5A and Stat5B, and can disrupt Stat5 DNA binding activity, consistent with a role of Y-343 as a site of recruitment to the receptor.
Journal ArticleDOI

Primary activation of interferon A and interferon B gene transcription by interferon regulatory factor 3.

TL;DR: IRF-3 and CBP/p300 are identified as integral components of the virus-induced complex that stimulates type 1 IFN gene transcription and implicates a novel mechanism by which adenovirus may overcome the antiviral effects of the IFN pathway.
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Mutant U5A cells are complemented by an interferon-alpha beta receptor subunit generated by alternative processing of a new member of a cytokine receptor gene cluster.

TL;DR: Together IFNAR2, CRFB4,IFNAR1 and AF1 form a cluster of class II cytokine receptor genes on human chromosome 21, establishing that together IFNARE2,CRFB4 and IFnAR2 form a clusters of class I cytokine receptors on human chromosomes 21.
Journal ArticleDOI

Cytokines in the Treatment of Cancer.

TL;DR: Current knowledge and clinical application of cytokines either as monotherapy or in combination with other biological agents are summarized and a discussion of future directions for research on these cytokines is emphasized to bring them to fruition as major contributors for the treatment of metastatic malignancy.
Journal ArticleDOI

Ciliary Neurotrophic Factor and Stress Stimuli Activate the Jak-STAT Pathway in Retinal Neurons and Glia

TL;DR: It is shown that STAT3 is activated in the retina after exposure to subtoxic bright light, mechanical trauma, and systemic administration of the α2-adrenergic agonist xylazine, all of which have been shown previously to condition photoreceptors to resist light-induced degeneration.
References
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Journal ArticleDOI

Stimulation of 3T3 cells induces transcription of the c- fos proto-oncogene

TL;DR: Transcription of the c-fos proto-oncogene is greatly increased within minutes of administering purified growth factors to quiescent 3T3 cells, and this stimulation is the most rapid transcriptional response to peptide growth factors yet described, implying a role for c- fos in cell-cycle control.
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Equilibria and kinetics of lac repressor-operator interactions by polyacrylamide gel electrophoresis

TL;DR: Gel electrophoresis in studies of equilibrium binding, site distribution, and kinetics of protein-DNA interactions found that binding to the so-called third operator site (03) is 15-18 fold weaker than operator binding, and that the binding reactions with the first and third operators are uncoupled, implying that there is no communication between the sites.
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Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6

TL;DR: A new family member, Stat3, becomes activated through phosphorylation on tyrosine as a DNA binding protein in response to epidermal growth factor and interleukin-6 but not interferon gamma (IFN-gamma).
Journal ArticleDOI

SH2 and SH3 Domains: Elements that Control Interactions of Cytoplasmic Signaling Proteins

TL;DR: Observations suggest that SH2 and SH3 domains participate in the control of intracellular responses to growth factor stimulation.
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A gel electrophoresis method for quantifying the binding of proteins to specific DNA regions: application to components of the Escherichia coli lactose operon regulatory system

TL;DR: It is demonstrated that even when pre-formed in the presence of CAP-cAMP, the polymerase-promoter open complex becomes unstable if CAP is then selectively removed, and this gel method is applied to the study of the E. coli lactose operon regulatory system.
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