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)

Heterotrimeric GTP-binding regulatory proteins (G proteins) have been identified as part of signal transduction systems in a wide variety of organisms. In this paper, we establish the presence of a G protein associated with the plasma membranes of the apical bud of etiolated peas. The GTPase activity is induced by low fluences of blue light administered to plasma membrane-enriched fractions. The activity is not responsive to red-light irradiation and is specific for GTP. The threshold for the excitation of the GTPase activity in vitro is less than 10(-1) mumol.m-2 of blue light, consistent with participation in the blue low-fluence system identified in the same tissue. A 40-kDa polypeptide is recognized by polyclonal antisera directed against the alpha subunit of the G protein transducin. The polypeptide also serves as a substrate for ADP-ribosylation by cholera and pertussis toxins. The ability of the 40-kDa polypeptide to serve as substrate for the toxin-mediated ribosylation is mediated by blue-light irradiation, implying that the 40-kDa polypeptide is the alpha subunit of a blue-light-stimulated G protein. The 40-kDa polypeptide binds a nonhydrolyzable photoaffinity-labeling analog of GTP only after irradiation with blue light. The protein we have described may function as an alpha subunit of a G protein active in the process of light-mediated development in higher plants.
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PMID:A blue-light-activated GTP-binding protein in the plasma membranes of etiolated peas. 192 52

Rat glioma C6 BU1 cells were treated in tissue culture with cholera toxin. Incubation of membranes derived from these cells with fresh cholera toxin and [32P]NAD+ failed to promote incorporation of radioactivity into polypeptides corresponding to forms of Gs alpha. This is generally assumed to reflect prior ADP ribosylation of these polypeptides in vivo using endogenous NAD+ as substrate. However, immunological studies with anti-peptide antisera which identify all forms of Gs alpha demonstrated that concentrations of this polypeptide were now substantially reduced in the membranes. This effect was specific for Gs alpha as neither the alpha-subunits of the pertussis toxin-sensitive G-proteins Gi2 and Gi3, nor the beta subunit common to the various G-proteins were lost in parallel. Pertussis toxin-catalysed ADP ribosylation did not cause the downregulation of Gs alpha nor of the alpha-subunits of Gi2 or Gi3 although it did cause ADP ribosylation of the entire complement of both Gi2 and Gi3 in the membranes. Despite the reduction in levels of immunoreactive Gs alpha from the membranes of cholera toxin-treated cells, no alterations in levels of mRNA corresponding to this G-protein were noted.
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PMID:Chronic exposure of rat glioma C6 cells to cholera toxin induces loss of the alpha-subunit of the stimulatory guanine nucleotide-binding protein (Gs). 211 2

Initially we established that the binding of collagen to human blood platelets stimulates both the rapid loss of PIP2 and the generation of inositol-4,5-bisphosphate (IP2) and inositol-1,4,5-triphosphate (IP3). These results indicate that the binding of collagen stimulates inositol phospholipid-specific phospholipase C during platelet activation. The fact that GTP or GTP-gamma-S augments, and pertussis toxin inhibits, collagen-induced IP3 formation suggests that a GTP-binding protein (or (or proteins) may be directly involved in the regulation of phospholipase C-mediated phosphoinositide turnover in human platelets. We have used several complementary techniques to isolate and characterize a platelet 41-kDa polypeptide (or polypeptides) that has a number of structural and functional similarities to the regulatory alpha i subunit of the GTP-binding proteins isolated from bovine brain. This 41-kDa polypeptide (or polypeptides) is found to be closely associated with at least four membrane glycoproteins (e.g., gp180, gp110, gp95, and gp75) in a 330-kDa complex that can be dissociated by treatment with high salt plus urea. Most important, we have demonstrated that antilymphoma 41-kDa (alpha i subunit of GTP-binding proteins) antibody cross-reacts with the platelet 41-kDa protein (or proteins) and the alpha i subunit of bovine brain Gi alpha proteins, and blocks GTP/collagen-induced IP3 formation. These data provide strong evidence that the 41-kDa platelet GTP-binding protein (or proteins) is directly involved in collagen-induced signal transduction during platelet activation.
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PMID:Membrane-associated 41-kDa GTP-binding protein in collagen-induced platelet activation. 211 41

A1-adenosine receptors and associated guanine nucleotide-binding proteins (G proteins) have been co-purified from bovine cerebral cortex by agonist affinity chromatography [J. Biol. Chem. 264:14853-14859 (1989)]. In this study we have reconstituted purified bovine brain A1 receptors into human platelet membranes that contain A2- but no detectable A1-adenosine receptors. The recovery of reconstituted receptors was assessed from the binding of the antagonist radioligand [125I]3-(4-amino-3-iodo)phenethyl-1-propyl-8-cyclopentyl-xanthine and ranged from 32 to 84%. Coupling of reconstituted A1 receptors to platelet G proteins was evaluated by measurement of the high affinity binding of an agonist radioligand, 125I-aminobenzyladenosine, to receptor-G protein complexes and by stereospecific photoaffinity labeling of a 35,000-Da receptor polypeptide with the agonist photoaffinity label 125I-azidobenzyladenosine. Fifty percent of receptors reconstituted into platelet membranes bound agonists with high affinity, indicative of coupling to platelet G proteins. Reconstituted A1 receptors bound various ligands with affinities characteristic of A1 receptors of bovine brain. Although platelets contain both pertussis toxin-sensitive and -insensitive G proteins, reconstituted high affinity agonist binding was almost completely abolished by treatment of platelet membranes with guanosine 5'-3-O-(thio)triphosphate, pertussis toxin, N-ethylmaleimide, or heparin. Following reconstitution, A1 receptors could be resolubilized in complexes with platelet G proteins. The data suggest that marked species differences in the binding affinity of ligands to adenosine receptors result from differences in the receptors rather than membrane structure or G proteins and, further, that A1 receptors couple selectively and tightly to pertussis toxin-sensitive G proteins.
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PMID:Interaction of purified bovine brain A1-adenosine receptors with guanine nucleotide-binding proteins of human platelet membranes following reconstitution. 211 48

Gs and Gi2 are G proteins whose alpha subunits are 65% homologous. Within the 355 amino acid alpha i2 polypeptide, substitution of residues Ile213-Lys319 with the corresponding alpha s region (Ile235-Arg356) generated a chimera that activated adenylyl cyclase, indicating that the alpha s activation domain resides within this 122 amino acid alpha s sequence. Mutation within alpha s residues Glu15-Pro144 resulted in an alpha s polypeptide having an enhanced rate of GDP dissociation. Mutation within two regions of the N-terminus influenced the ability of pertussis toxin to ADP-ribosylate the alpha subunit polypeptide, a reaction controlled by the beta gamma subunit complex. The findings define the G protein alpha subunit N-terminus as a regulatory region controlling beta gamma subunit interactions and GDP dissociation independent of the GTPase and effector activation domains.
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PMID:G alpha i-G alpha s chimeras define the function of alpha chain domains in control of G protein activation and beta gamma subunit complex interactions. 212 66

Treatment of neuroblastoma x glioma hybrid, NG108-15, cells with prostaglandin E1, which in these cells activates adenylate cyclase, produced a marked (50%) reduction in immunologically detectable levels of Gs alpha associated with the plasma membrane. This effect was dependent both on the time of treatment and on the concentration of the receptor ligand used and did not involve a translocation of Gs alpha from the membrane to the cytoplasm of the cells. Both the 45- and 42-kDa forms of Gs alpha which are expressed by these cells were reduced in levels by treatment with the agonist but the greater effect was on the more prevalent 45-kDa polypeptide. By contrast, treatment of the cells with forskolin over the same period did not produce a reduction in levels of Gs alpha, indicating that the effect of prostaglandin E1 was independent of cAMP production. Prostaglandin E1-mediated down-regulation of Gs alpha levels was not produced at the transcriptional level as amounts of mRNA encoding Gs alpha were not reduced by treatment of the cells with agonist. Further, treatment of NG108-15 cells with cycloheximide, throughout the time period required to produce maximal prostaglandin E1-dependent down-regulation of Gs alpha, demonstrated that complete suppression of de novo protein synthesis could not mimic the effect of prostaglandin E1 and hence even complete inhibition of transcription of the Gs alpha gene and/or translation of pre-existing mRNA could not account for these results. Prostaglandin E1 treatment of the cells had no effect on steady-state levels of the alpha subunits of the pertussis toxin-sensitive G-proteins, Gi2, Gi3, Go, which are expressed by these cells or on the level of G-protein beta subunit. Fluoride stimulation of adenylate cyclase activity in membranes of S49 cyc- cells following addition of sodium cholate extracts of membranes of prostaglandin E1-treated NG108-15 cells was only some 50% as effective as with equivalent extracts from untreated cells. These results provide evidence for a novel mechanism of receptor-mediated control of the stimulation of adenylate cyclase, involving reduction in the steady-state amounts of Gs alpha.
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PMID:Prostaglandin E1-mediated, cyclic AMP-independent, down-regulation of Gs alpha in neuroblastoma x glioma hybrid cells. 217 Mar 66

Three distinct antipeptide antisera generated against synthetic peptides that represent parts of the primary sequence of the alpha-subunit of the (pertussis toxin-sensitive) guanine nucleotide binding protein G0 were used in two-dimensional immunoblots of membranes of neuroblastoma X glioma (NG108-15) cells. Each antiserum identified two distinct polypeptides of some 39 kDa. These had apparent isoelectric points of 5.5 and 5.8. Differentiation of NG108-15 cells in response separately to dibutyryl cyclic AMP (cAMP), 8-bromo cAMP, forskolin, and prostaglandin E1 produced elevated levels of G0 alpha, as has previously been noted in one-dimensional immunoblots. Two-dimensional analysis demonstrated that the cAMP-induced increases in levels of G0 alpha were only of the more acidic isoform. The two isoforms were both substrates for pertussis toxin-catalysed ADP-ribosylation and did not appear to represent differentially phosphorylated forms of the same polypeptide. Separation of the two forms of G0 alpha could be achieved in one-dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis when 4 M deionized urea was included in the resolving gel. The more slowly migrating band was the acidic form and corresponded exactly in mobility with the major form of G0 from both rat and mouse brain. There was no equivalent in brain of the more rapidly migrating form of G0 from the cells. In agreement with the data from two-dimensional gels, only the more slowly migrating form was expressed in considerably higher amounts following cAMP-induced differentiation of NG108-15 cells. Of these two forms of "G0," the acidic species is equivalent to G0 from brain, but the basic form is not identical with G0*, which has been purified from bovine brain.
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PMID:Identification of two distinct isoforms of the guanine nucleotide binding protein G0 in neuroblastoma X glioma hybrid cells: independent regulation during cyclic AMP-induced differentiation. 217 64

Quiescent cultures of Swiss 3T3 cells can be stimulated to recommence DNA synthesis by polypeptide growth factors, neuropeptides, and various pharmacologic agents that act via multiple signal transduction pathways. Neuropeptides of the bombesin family provide potent mitogens to elucidate these pathways. These peptides bind to specific receptors that have been characterized by radioligand binding and sensitivity to antagonists and identified as glycoproteins with a Mr of 75,000-85,000 by chemical cross-linking. After binding, bombesin elicits a cascade of early molecular events including stimulation of phosphorylation of the acidic Mr 80,000 cellular protein, which is a major substrate of protein kinase C; Ca2+ mobilization mediated by Ins(1,4,5)P3, Na+ and K+ fluxes, transmodulation of EGF receptor, enhancement of cAMP accumulation, and expression of the proto-oncogenes c-fos and c-myc. Studies using membrane preparations and permeabilized 3T3 cells indicate that G proteins play a role in the transduction of the mitogenic signal triggered by the binding of bombesin to its receptor. A pertussis toxin-insensitive G protein couples the bombesin receptor to the generation of a signal that activates protein kinase C, whereas a pertussis toxin-sensitive G protein mediates cross-talk between transmembrane signaling pathways. Bombesin-mediated mitogenesis can be blocked by different antagonists and by interrupting the signal-transduction process at various postreceptor levels. Thus, prolonged treatment with vasopressin causes heterologous desensitization to the mitogenic action of bombesin. This mitogenic block is mediated by uncoupling the receptor from its signaling system. Loss of responsiveness to bombesin-stimulated DNA synthesis is also induced by down-regulation of protein kinase C.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bombesin stimulation of mitogenesis. Specific receptors, signal transduction, and early events. 217 58

Rabbit antiserum and murine monoclonal antibodies were raised against a strain of Haemophilus ducreyi. The antiserum gave high immunofluorescence titres and strong dot blot reactions with all H. ducreyi strains tested and the only cross reaction was with Bordetella pertussis. Three monoclonal antibodies, all of isotype IgG2a, also gave high immunofluorescence titres with H. ducreyi but did not cross react with any other species tested. Immunoblotting showed the monoclonal antibodies to react with a single polypeptide band of mol. wt 29,000 in the outer-membrane fraction of H. ducreyi. These antibodies have potential for use as diagnostic reagents and for investigating the pathogenicity of H. ducreyi.
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PMID:The production and characterisation of rabbit antiserum and murine monoclonal antibodies to Haemophilus ducreyi. 217 58

The extracellular calmodulin-sensitive adenylate cyclase produced by Bordetella pertussis is synthesized as a 215-kDa precursor. This polypeptide is transported to the outer membrane of the bacteria where it is proteolytically processed to a 45-kDa catalytic subunit which is released into the culture supernatant [Masure, H.R., & Storm, D.R. (1989) biochemistry 28, 438-442]. The gene encoding this enzyme, cyaA, is part of the cya operon that also includes the genes cyaB, cyaD, and cyaE. A comparison of the predicted amino acid sequences encoded by cyaA, cyaB, and cyaD with the amino acid sequences encoded by hlyA, hlyB, and hlyD genes from the hemolysin (hly) operon from Escherichia coli shows a large degree of sequence similarity [Glaser, P., Sakamoto, H., Bellalou, J., Ullmann, A., & Danchin, A. (1988) EMBO J. 7, 3997-4004]. Complementation studies have shown that HlyB and HlyD are responsible for the secretion of HlyA (hemolysin) from E. coli. The signal sequence responsible for secretion of hemolysin has been shown to reside in its C-terminal 27 amino acids. Similarly, CyaB, CyaD, and CyaE are required for the secretion of CyaA from Bordetella pertussis. We placed the cyaA gene and a truncated cyaA gene that lacks the nucleotides that code for a putative C-terminal secretory signal sequence under the control of the lac promoter in the plasmid pUC-19. These plasmids were transformed into strains of E. coli which contained the hly operon. The truncated cyaA gene product, lacking the putative signal sequence, was not secreted but accumulated inside the cell.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Secretion of the Bordetella pertussis adenylate cyclase from Escherichia coli containing the hemolysin operon. 218 14


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