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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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White Spot Syndrome Virus Annexes a Shrimp STAT To Enhance Expression of the Immediate-Early Gene ie1

TL;DR: It is shown that white spot syndrome virus (WSSV) uses a shrimp STAT as a transcription factor to enhance viral gene expression in host cells and annexes a putative shrimp defense mechanism, which it uses to enhance the expression of viral immediate-early genes.
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Synergistic activation of NF-kappaB by tumor necrosis factor alpha and gamma interferon via enhanced I kappaB alpha degradation and de novo I kappaBbeta degradation.

TL;DR: Cotreatment of cells with TNF-alpha and IFN-gamma leads to persistent activation of NF-kappaB and to potent activation of kappaB-dependent gene expression, which may explain, at least in part, the synergy observed between these cytokines, as well as their involvement in the generation of an effective immune response.
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Evaluation of potential Stat3-regulated genes in human breast cancer.

TL;DR: The results suggest that constitutive Stat3 signaling may be one of the key upstream regulators to induce these downstream proteins, which may play important roles in Stat3-mediated oncogenesis in breast cancer.
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Phosphorylated interferon-alpha receptor 1 subunit (IFNaR1) acts as a docking site for the latent form of the 113 kDa STAT2 protein.

TL;DR: It is demonstrated that, in vitro, p135tyk2 phosphorylates two tyrosines on IFNaR1, a phosphopeptide corresponding to the major phosphorylation site (Tyr466) binds STAT2, but not STAT1, in an SH‐2‐dependent manner, consistent with a model in which IF NaR1 mediates the interaction between JAK kinases and the STAT transcription factors.
Journal ArticleDOI

Src Kinases Mediate STAT Growth Pathways in Squamous Cell Carcinoma of the Head and Neck

TL;DR: A role for Src kinases in mediating activation of STATs 3 and 5 in concert with the EGFR in SCCHN cells is demonstrated and strategies to target Src activation may contribute to the treatment of cancers that demonstrate increased levels of EGFR and STATs.
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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