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.read more
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PatentDOI
Platinum compounds that inhibit constitutive stat3 signaling and induce cell cycle arrest and apoptosis of malignant cells
TL;DR: These findings provide evidence for the inhibition of Stat3 activity and biological functions by IS3 295 through interaction with Stat3 protein and suggests potential new applications for platinum (IV) complexes as modulators of the Stat3 pathway for cancer therapy.
Journal ArticleDOI
SOCS-1/SSI-1-Deficient NKT Cells Participate in Severe Hepatitis through Dysregulated Cross-Talk Inhibition of IFN-γ and IL-4 Signaling In Vivo
Tetsuji Naka,Hiroko Tsutsui,Minoru Fujimoto,Yoshinori Kawazoe,Hidetsugu Kohzaki,Yoshiaki Morita,Nakagawa,Masashi Narazaki,Keishi Adachi,Tomohiro Yoshimoto,Kenji Nakanishi,Tadamitsu Kishimoto +11 more
TL;DR: It is suggested that SOCS-1 deficiency-induced persistent activation of STAT1 and STAT6, which would be inhibited by SOCs-1 under normal conditions, may induce abnormal activation of NKT cells, thus leading to lethal pathological changes in SOCS -1-deficient mice.
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Molecular determinants of retinal ganglion cell development, survival, and regeneration
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Journal ArticleDOI
Interferon gamma and interleukin 4 stimulate prolonged expression of inducible nitric oxide synthase in human airway epithelium through synthesis of soluble mediators.
Fuhua H. Guo,Kohsaku Uetani,S. J. Haque,Bryan R.G. Williams,Raed A. Dweik,Frederik B. J. M. Thunnissen,William J. Calhoun,Serpil C. Erzurum +7 more
TL;DR: A combination of IFNgamma/ IL-4, which occurs naturally in the lung epithelial lining fluid, leads to maintenance of iNOS expression in human airway epithelium through production of soluble mediators and stabilization of mRNA.
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The Role of IFN-γ and TNF-α-Responsive Regulatory Elements in the Synergistic Induction of Indoleamine Dioxygenase
TL;DR: Nuclear concentrations of signal transducer and activator of transcription-1 and IFN regulatory factor-1, transcription factors that bind gamma-activated sequences (GAS) andIFN-stimulated response elements (ISRE), respectively, were found to increase after stimulation with IFN-γ and TNF-αrelative to stimulation with individual cytokines.
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
Michael Fried,Donald M. Crothers +1 more
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
Mark M. Garner,Arnold Revzin +1 more
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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