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 CAMP reaction is a synergistic lysis of erythrocytes by the interaction of an extracellular protein (CAMP factor) produced by some streptococcal species with the Staphylococcus aureus sphingomyelinase C (beta-toxin). Group A streptococci (GAS [Streptococcus pyogenes]) have been long considered CAMP negative, and this reaction commonly has been used to distinguish GAS from Streptococcus agalactiae. We here provide evidence that GAS possess this gene and produce an extracellular CAMP factor capable of participating in a positive CAMP reaction. The S. pyogenes CAMP factor is specified by a 774-bp open reading frame homologous to the CAMP factor genes from S. agalactiae and Streptococcus uberis. This gene, designated cfa, was isolated on a 1,256-bp fragment and cloned in Escherichia coli. Recombinant clones of E. coli expressing cfa secreted an active CAMP factor. The deduced 28.5-kDa protein encoded by cfa consists of 257 amino acids, with a predicted 28-amino-acid signal peptide. The cfa gene is widely spread among GAS: 82 of 100 clinical GAS isolates produced a positive CAMP reaction. Of the CAMP-negative strains, 17 of the 18 GAS strains contained the cfa gene. Additionally, CAMP activity was detected in streptococci from serogroups C, M, P, R, and U. The cfa gene was cloned and actively expressed in Escherichia coli and gene fusions were made, placing the beta-galactosidase gene (lacZ) under control of the cfa promoter. These cfa promoter-lacZ fusions were introduced into S. pyogenes via a bacteriophage-derived site-specific integration vector where they showed that the cfa gene has a strong promoter that may be subject to as-yet-unidentified regulatory factors. The results presented here, along with previous reports, indicate that the CAMP factor gene is fairly widespread among streptococci, being present at least in groups A, B, C, G, M, P, R, and U.
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PMID:Identification, cloning, and expression of the CAMP factor gene (cfa) of group A streptococci. 1045 23

The vasoactive intestinal peptide (VIP) and the pituitary adenylate cyclase-activating polypeptide (PACAP), two immunomodulatory neuropeptides that affect both innate and acquired immunity, down-regulate IL-12 p40 and inducible NO synthase expression in LPS/IFN-gamma-stimulated macrophages. We showed previously that VIP/PACAP inhibit NF-kappaB nuclear translocation through the stabilization of IkappaB and reduce IFN regulatory factor-1 (IRF-1) binding to the regulatory elements found in the IL-12 p40 and inducible NO synthase promoters. In this paper we studied the molecular mechanisms involved in the VIP/PACAP regulation of IRF-1 transactivating activity. Our studies indicate that the inhibition in IRF-1 binding correlates with a reduction in IRF-1 protein and mRNA in IFN-gamma-treated Raw 264.7 macrophages. In agreement with the described Janus kinase (Jak)1/Jak2/STAT1/IRF-1 activation pathway, VIP/PACAP inhibit Jak1/Jak2, STAT1 phosphorylation, and the binding of STAT1 to the GAS sequence motif in the IRF-1 promoter. The effects of VIP/PACAP are mediated through the specific VIP/PACAP receptor-1 and the cAMP/protein kinase A (PKA) transduction pathway, but not through the induction of suppressor of cytokine signaling-1 or suppressor of cytokine signaling-3. Because IFN-gamma is a major stimulator of innate immune responses in vivo, the down-regulation of IFN-gamma-induced gene expression by VIP and PACAP could represent a significant element in the regulation of the inflammatory response by endogenous neuropeptides.
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PMID:Inhibition of IFN-gamma-induced janus kinase-1-STAT1 activation in macrophages by vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide. 1097 15

Aromatase is the terminal enzyme responsible for estrogen biosynthesis in mammals; it is present in various testicular cells including germ cells. The aromatase gene (Cyp19) is unique in humans and its expression is regulated in a tissue and more precisely, in a cell-specific manner via the alternative use of various promoters located in the first exon. Nevertheless, there is little information concerning the regulation of the testicular aromatase especially in germ cells. This prompted us to study the control of Cyp19 gene expression and its role in the regulation of the testicular androgen/estrogen ratio. Gonadotrophins and cAMP modulate aromatase expression in somatic cells which confirms that promoter II is controlled via CRE. Moreover, we have demonstrated that in highly purified germ cells from adult rats (pachytene spermatocytes and round spermatids), transforming growth factor beta (TGFbeta) inhibited the expression of Cyp19 in both germ cell types. In contrast, tumor necrosis factor alpha (TNFalpha) stimulated Cyp19 expression in pachytene spermatocytes. The effect of TNFalpha is amplified in presence of dexamethasone. Therefore, we suggest that in germ cells, TNFalpha enhances expression of aromatase through promoter PI.4 in pachytene spermatocytes, possibly via an AP1 site upstream the GAS element, while in round spermatids TNF requires glucocorticoids as a co-stimulator to increase Cyp19 gene expression. In addition, we have shown that androgens and estrogens by themselves modulate Cyp19 gene expression in all testicular cell types studied suggesting the presence of ARE and ERE on the Cyp19 gene promoter(s). Finally, in presence of seminiferous tubules or Sertoli cell-conditioned media, aromatase transcripts are increased in both Leydig cells and germ cells suggesting that other locally produced modulators (e.g. LRH-1) are involved in the regulation of the aromatase gene expression especially in Leydig cells. Using RACE (Rapid Amplification of cDNA Ends)-PCR, we have confirmed that promoter II mainly directs expression of the aromatase gene in all testicular cell types studied in the rat. However, involvement of another promoter such as PI.4 is suggested as well.
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PMID:The promoter(s) of the aromatase gene in male testicular cells. 1509 93

Previous studies demonstrated that mice with a null mutation in the gene encoding the hormone gastrin have impaired gastric acid secretion. Hence, the aim of this study was to evaluate changes in the acid-secreting parietal cell in gastrin-deficient (GAS-KO) mice. Analysis of several transcripts encoding parietal cell proteins involved in gastric acid secretion showed reduced abundance in the GAS-KO stomach, including H+,K+-ATPase alpha- and beta-subunits, KCNQ1 potassium channel, aquaporin-4 water channel, and creatine kinase B, which were reversed by gastrin infusion for 1 wk. Although mRNA and protein levels of LIM and SH3 domain-containing protein-1 (LASP-1) were not greatly changed in the mutant, there was a marked reduction in phosphorylation, consistent with its proposed role as a cAMP signal adaptor protein associated with acid secretion. A more comprehensive analysis of parietal cell gene expression in GAS-KO mice was performed using the Affymetrix U74AV2 chip with RNA from parietal cells purified by flow cytometry to >90%. Comparison of gene expression in GAS-KO and wild-type mice identified 47 transcripts that differed by greater than or equal to twofold, suggesting that gastrin affects parietal cell gene expression in a specific manner. The differentially expressed genes included several genes in signaling pathways, with a substantial number (20%) known to be target genes for Wnt and Myc.
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PMID:Gene expression profiling of gastrin target genes in parietal cells. 1627 79

To develop intracellularly within phagocytes and cause chronic infection, Brucella must overcome different steps of the host immune responses. IFNgamma is a key mediator of the innate and adaptive responses produced during Brucella infection. Therefore, Brucella would control host defenses by impairing macrophage responses to IFNgamma. We first showed that in infected human macrophages (VD3-differentiated THP-1 cells) Brucella escaped the microbicidal environment generated by IFNgamma. We then analyzed the IFNgamma-mediated signaling in Brucella-infected cells. We observed no decrease in STAT1 tyrosine or serine phosphorylation, or in dimerization of phosphorylated STAT1 (P-STAT1) and P-STAT1 translocation to the nucleus or in P-STAT1 binding to GAS, a minimal IFNgamma-response DNA sequence. In contrast, immuno-precipitation experiments indicated that the IFNgamma-mediated association of P-STAT1 with CBP/P300 transactivators was markedly reduced in infected macrophages, demonstrating that P-STAT1 was unable to normally recruit these transactivators. The host cell cAMP pathway triggered by Brucella could be responsible for this defect, CBP/P300 mobilization by phosphorylated CREB (P-CREB) disrupting the IFNgamma-induced STAT1-CBP/P300 association, required for a normal response of macrophages to IFNgamma. In any case, the inhibition of an essential protein-protein interaction probably lead to a deteriorated response to IFNgamma and thus participated in the pathogen's establishment within its host.
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PMID:The IFNgamma-induced STAT1-CBP/P300 association, required for a normal response to the cytokine, is disrupted in Brucella-infected macrophages. 1904 14