Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bordetella pertussis, the causative agent of whooping cough, produces a wide array of factors that are associated with its ability to cause disease. The expression and regulation of these virulence factors is dependent upon the bvg locus (originally designated the vir locus), which encodes two proteins: BvgA, a 23-kDa cytoplasmic protein, and BvgS, a 135-kDa transmembrane protein. It is proposed that BvgS responds to environmental signals and interacts with BvgA, a transcriptional regulator which upon modification by BvgS binds to specific promoters and activates transcription. An additional class of genes is repressed by the bvg locus. Expression of this class, the bvg-repressed genes (vrgs [for vir-repressed genes]), is reduced under conditions in which expression of the aforementioned bvg-activated virulence factors is maximal; this repression is dependent upon the presence of an intact bvgAS locus. We have previously identified a locus required for regulation of all of the known bvg-repressed genes in B. pertussis. This locus, designated bvgR, maps to a location immediately downstream of bvgAS. We have undertaken deletion and complementation studies, as well as sequence analysis, in order to identify the bvgR open reading frame and identify the cis-acting sequences required for regulated expression of bvgR. Studies utilizing transcriptional fusions of bvgR to the gene encoding alkaline phosphatase have demonstrated that bvgR is activated at the level of transcription and that this activation is dependent upon an intact bvgAS locus.
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PMID:Characterization of the bvgR locus of Bordetella pertussis. 953 63

The 7-pass transmembrane protein Smoothened was investigated for its ability to act as a G-protein-coupled receptor in Xenopus laevis melanophores. A plasmid containing the human Smoothened cDNA insert was transfected into immortalized frog pigment cells. Cells expressing the protein showed a phenotype of persistent pigment aggregation, a hallmark of constitutive Galpha(i) activation. Smoothened-mediated pigment aggregation was reversed by treatment with pertussis toxin or by co-expression with dominant negative Galpha(i). The ability of melanophores to express functional Smoothened was also determined by its co-expression with the twelve-pass transmembrane protein, Patched. Patched blocked Smoothened-mediated melanosome aggregation in a dose-dependent manner, consistent with its physiological role as an inhibitor of Smoothened. That the reconstituted Patched-Smoothened receptor complex functions normally in pigment cells was demonstrated by co-transfection with the activating ligand, Sonic hedgehog, as well as by direct application of the recombinant Sonic hedgehog protein. Sonic hedgehog reversed Patched-mediated inhibition of Smoothened and induced pigment aggregation. The findings demonstrate that the human Sonic hedgehog receptor complex can be functionally reconstituted in melanophores and that it is capable of transmembrane signaling by utilizing endogenous Galpha(i).
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PMID:Smoothened activates Galphai-mediated signaling in frog melanophores. 1083 29

Bordetella pertussis, the causative agent of whooping cough, produces a wide array of factors that are associated with its ability to cause disease. The expression and regulation of these virulence factors are dependent upon the bvg locus, which encodes three proteins: BvgA, a 23-kDa cytoplasmic protein; BvgS, a 135-kDa transmembrane protein; and BvgR, a 32-kDa protein. It is hypothesized that BvgS responds to environmental signals and interacts with BvgA, a transcriptional regulator, which upon modification by BvgS binds to specific promoters and activates transcription. An additional class of genes is repressed by the products of the bvg locus. The repression of these genes is dependent upon the third gene, bvgR. Expression of bvgR is dependent upon the function of BvgA and BvgS. This led to the hypothesis that the binding of phosphorylated BvgA to the bvgR promoter activates the expression of bvgR. We undertook an analysis of the transcriptional activation of bvgR expression. We identified the bvgR transcript by Northern blot analysis and identified the start site of transcription by primer extension. We determined that transcriptional activation of the bvgR promoter in an in vitro transcription system requires the addition of phosphorylated BvgA. Additionally, we have identified cis-acting regions that are required for BvgA activation of the bvgR promoter by in vitro footprinting and in vivo deletion and linker scanning analyses. A model of BvgA binding to the bvgR promoter is presented.
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PMID:Analysis of bvgR expression in Bordetella pertussis. 1461 54

The ferric citrate transport system of Escherichia coli is the first example of a transcription initiation mechanism that starts at the cell surface. The inducer, ferric citrate, binds to an outer membrane transport protein, and without further transport elicits a signal that is transmitted across the outer membrane, the periplasm, and the cytoplasmic membrane into the cytoplasm. Signal transfer across the three subcellular compartments is mediated by the outer membrane transport protein that interacts in the periplasm with a cytoplasmic transmembrane protein. The latter is required for activation of a sigma factor which belongs to the extracytoplasmic function sigma factor family. A similar kind of transcription regulation has been demonstrated in Pseudomonas putida, P. aeruginosa, Serratia marcescens, Klebsiella pneumoniae, Aerobacter aerogenes, Bordetella pertussis, B. bronchseptica, B. avium, and Ralstonia solanacearum. The genomes of P. putida, P. aeruginosa, Nitrosomonas europaea, Bacteroides thetaiotaomicron and Caulobacter crescentus predict the existence of many more such transcriptional regulatory devices.
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PMID:Transmembrane transcriptional control (surface signalling) of the Escherichia coli Fec type. 1610 97

Rapid, progestin actions initiated at the cell surface that are often nongenomic have been described in a variety of reproductive tissues, but until recently the identities of the membrane receptors mediating these nonclassical progestins actions remained unclear. Evidence has been obtained in the last 4-5 years for the involvement of two types of novel membrane proteins unrelated to nuclear steroid receptors, progesterone membrane receptors (mPRs) and progesterone receptor membrane component 1 (PGMRC1), in progestin signaling in several vertebrate reproductive tissues and in the brain. The mPRs, (M(W) approximately 40 kDa) initially discovered in fish ovaries, comprise at least three subtypes, alpha, beta and gamma and belong to the seven-transmembrane progesterone adiponectin Q receptor (PAQR) family. Both recombinant and wildtype mPRs display high affinity (K(d) approximately 5 nM), limited capacity, displaceable and specific progesterone binding. The mPRs are directly coupled to G proteins and typically activate pertussis-sensitive inhibitory G proteins (G(i)), to down-regulate adenylyl cyclase activity. Recent studies suggest the alpha subtype (mPRalpha) has important physiological functions in variety of reproductive tissues. The mPRalpha is an intermediary in progestin induction of oocyte maturation and stimulation of sperm hypermotility in fish. In mammals, the mPRalphas have been implicated in progesterone regulation of uterine function in humans and GnRH secretion in rodents. The single-transmembrane protein PGMRC1 (M(W) 26-28 kDa) was first purified from porcine livers and its cDNA was subsequently cloned from porcine smooth muscle cells and a variety of other tissues by different investigators. PGMRC1 and the closely-related PGMRC2 belong to the membrane-associated progesterone receptor (MAPR) family. The PGMRC1 protein displays moderately high binding affinity for progesterone which is 2- to 10-fold greater than that for testosterone and glucocorticoids, and also can bind to other molecules such as heme, cholesterol metabolites and proteins. The signal transduction pathways induced by binding of progesterone to PGMRC1 have not been described to date, although motifs for tyrosine kinase, kinase binding, SH2 and SH3 have been predicted from the amino acid sequence. Evidence has been obtained that PGMRC1 mediates the antiapoptotic affects of progesterone in rat granulosa cells. The PGMRC1 protein may also be an intermediary in the progesterone induction of the acrosome reaction in mammalian sperm. Despite these recent advances, many aspects of progestin signaling through these two families of novel membrane proteins remain unresolved. Biochemical characterization of the receptors has been hampered by rapid degradation of the partially purified proteins. A major technical challenge has been to express sufficient amounts of the recombinant receptors on the plasma membranes in eukaryotic systems to permit investigations of their progestin binding and signal transduction characteristics. Additional basic information on the molecular and cellular mechanisms by which mPRs and PGMRC1 interact with progestins, signal transductions pathways and other proteins will be required to establish a comprehensive model of nontraditional progestin actions mediated through these novel proteins.
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PMID:Characteristics of membrane progestin receptor alpha (mPRalpha) and progesterone membrane receptor component 1 (PGMRC1) and their roles in mediating rapid progestin actions. 1834 88

The chemokine receptor CXCR6 and its ligand CXCL16 are involved in inflammation. Thus far, they were known to be expressed mainly by T cells and macrophages, respectively. However, we detected both in all of 170 human primary mammary carcinomas and at similar levels in all 8 human mammary carcinoma cell lines tested by microarray analysis. Expression was confirmed by reverse transcription-PCR and for the cell lines also by fluorescence-activated cell sorting analysis. CXCR6 and CXCL16 were also detected in several mouse and human mammary, colon, and pancreatic carcinoma cell lines. CXCL16 is a transmembrane protein from which the soluble chemokine can be cleaved off. The transmembrane form is present on the surface of the carcinoma cells. Surprisingly, suppression of either CXCR6 or CXCL16 led to greatly enhanced proliferation in vitro as well as in vivo, indicating that their interaction inhibits proliferation. This notion was verified using inhibitory antibodies and by introduction of CXCL16 into a rare CXCL16-negative cell line. The effect was mediated by the G protein-coupled receptor CXCR6 because it was blocked by the G(i) protein inhibitor pertussis toxin. In contrast, the soluble CXCL16 chemokine enhanced proliferation, and this was also mediated by CXCR6 but not via G(i) protein. It is remarkable that both CXCR6 and CXCL16 are expressed by all mammary carcinomas because cells that lose either acquire a growth advantage and should be selected during tumor progression. This suggests an unknown important role in tumor formation. Proteases, possibly macrophage derived, might convert inhibitory transmembrane CXCL16 into the stimulatory chemokine.
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PMID:The chemokine receptor CXCR6 and its ligand CXCL16 are expressed in carcinomas and inhibit proliferation. 2124 92