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Journal ArticleDOI

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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Citations
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Journal ArticleDOI

Interferons and progesterone for establishment and maintenance of pregnancy: interactions among novel cell signaling pathways.

TL;DR: Understanding the roles of IFNs and ISGs in uterine receptivity for implantation is necessary to develop strategies to enhance reproductive health and fertility in humans and domestic animals.
Journal ArticleDOI

Transcription factors that regulate monocyte/macrophage differentiation.

TL;DR: This work reviews the contribution of several transcription factors to the control of macrophage development and concludes that the transcription factor PU.1 has a critical role in this process.
Journal ArticleDOI

Jak3 Is Associated with CD40 and Is Critical for CD40 Induction of Gene Expression in B Cells

TL;DR: It is shown that engagement of CD40 induces tyrosine phosphorylation and activation of Jak3 as well as of STAT3, which indicates that signaling through Jak3 is activated by CD40 and plays an important role in CD40-mediated functions.
Book ChapterDOI

The Janus Protein Tyrosine Kinase Family and Its Role in Cytokine Signaling

TL;DR: It can be hypothesized that Jaks and Stats, if important for proliferation and differentiation, may be the targets for malignant transformation.
Journal ArticleDOI

Ser727-dependent recruitment of MCM5 by Stat1α in IFN-γ-induced transcriptional activation

TL;DR: It is shown that the C‐terminus of Stat1α is an independent TAD which can interact with a specific group of nuclear proteins and is recruited through interaction with MCM5 in a Ser727‐ and Leu724‐dependent manner to play a role in optimal transcriptional activation.
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.
Journal ArticleDOI

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.
Journal ArticleDOI

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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