Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.2.3.23 (GAS)
 957 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activation of natural killer cells and induction of cytotoxicity are complex processes whose molecular mechanisms have not been clearly elucidated. Stimulation of the NKL human NK cell line with interleukin-2 (IL-2) or protein-bound polysaccharide K (PSK) leads to sustained growth and cytolytic activity in comparison to unstimulated NKL cells. However, it is not known whether both agents give rise to the same or different intracellular signals. To determine the molecular basis for the action of IL-2 and PSK, the binding activity of AP-1, CRE, NF-kappaB, PU.1, SP-1, NFAT, STAT1, STAT5/6, GAS/ISRE and IRF-1 transcription factors was compared in IL-2- and PSK-stimulated NKL cells. Here we report that PSK enhanced AP-1 and CRE binding activities, whereas IL-2 increased AP-1 and SP-1 and modified GAS/ISRE, IRF-1 and STAT5. Our results indicate that IL-2 and PSK regulate different nuclear transcription factors in NKL cells, and that the signal transduction pathway used by these inducers is different.
 ...
PMID:Protein-bound polysaccharide K and interleukin-2 regulate different nuclear transcription factors in the NKL human natural killer cell line. 1145 71

Previous studies from our laboratory have shown that fulminant hepatitis caused by the mouse hepatitis virus, MHV-3, is dependent on production of the novel immune coagulant fgl2/fibroleukin. In this study, we investigate the role of IFN-gamma and TNF-alpha in the induction of fgl2 expression and fgl2-dependent hepatic apoptosis. Infusion of IFN-gamma in combination with TNF-alpha through the portal vein of fgl2+/+ mice led to widespread hepatic apoptosis and fibrin deposition. Livers from fgl2-/- mice were normal, although strong expression of the fgl2 knockout reporter gene Lac Z was seen in both resident hepatic macrophages and endothelial cells. In vitro, IFN-gamma and TNF-alpha induced fgl2 expression in a macrophage and endothelial cell-specific manner. In macrophages (peritoneal and RAW 264.7 cells), IFN-gamma, but not IFN-alpha, LPS, TNF-alpha, or IL-1 induced fgl2 mRNA transcription and protein expression, while in endothelial cells TNF-alpha, but not IFN-gamma, induced fgl2 transcription. In addition, while TNF-alpha enhanced IFN-gamma-induced macrophage fgl2 transcription, IFN-gamma also enhanced TNF-alpha-induced endothelial cell fgl2 transcription. The induction of fgl2 by IFN-gamma in macrophages involved a STAT1-dependent pathway, involving the composite cis elements Sp1/Sp3 and GAS/PU.1. The latter interacted with IFN-gamma-dependent Sp1/Sp3, STAT1, and the ETS family of transcription factors member PU.1. The interaction of PU.1 with the IFN-gamma-activated sequence/ETS family of transcription factors site determined the macrophage-specific induction of fgl2 by IFN-gamma. Overall, this study demonstrates that IFN-gamma and TNF-alpha induce hepatocyte apoptosis in vivo, which is dependent on induction of fgl2, and defines the molecular basis of transcription of fgl2 in vitro.
 ...
PMID:Cytokine-induced hepatic apoptosis is dependent on FGL2/fibroleukin: the role of Sp1/Sp3 and STAT1/PU.1 composite cis elements. 1670 65