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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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Nucleocytoplasmic shuttling by nucleoporins Nup153 and Nup214 and CRM1-dependent nuclear export control the subcellular distribution of latent Stat1.

TL;DR: It is proposed that two independent translocation pathways cooperate to determine the steady-state distribution of Stat1, and it is revealed that constitutive nucleocytoplasmic shuttling of Stat 1 is mediated by direct interactions with the FG repeat regions of nucleoporin 153 and nucleoparin 214 of the nuclear pore.
Journal ArticleDOI

Galectin-3 Exerts Cytokine-Like Regulatory Actions through the JAK–STAT Pathway

TL;DR: It is shown that galectin-3 exerts cytokine-like regulatory actions in rat and mouse brain-resident immune cells and significantly induced phosphorylation of STATs in glial cells from IFN–γ–deficient mice, suggesting that IFN-γ does not mediate activation ofSTATs.
Journal ArticleDOI

Enhancement of antiproliferative activity of gamma interferon by the specific inhibition of tyrosine dephosphorylation of Stat1.

TL;DR: It is suggested that the N-terminal domains ofSTATs are crucial for modulating STAT activities through regulating the tyrosine dephosphorylation of STATs.
Journal ArticleDOI

Mining for JAK-STAT mutations in cancer.

TL;DR: The Janus kinase-signal transducer and activator of transcription pathway mediates signaling by cytokines, which control survival, proliferation and differentiation of several cell types, and recent discoveries suggest that mutated JAK proteins will be potent targets for anti-cancer therapy.
Journal Article

Inhibition of interferon gamma signaling by the short chain fatty acid butyrate.

TL;DR: Butyrate negatively regulates mucosal inflammation through the inhibition of IFN-;/STAT1 signaling, and abnormal activity of STAT1 is associated with human malignancies and intestinal inflammatory diseases.
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.
Journal ArticleDOI

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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