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

Most Serratia marcescens strains produce a new type of cytolysin (hemolysin) which is also found in other Serratia species. The hemolytic polypeptide ShlA (M(r) 162 101) is secreted across the outer membrane through the help of the ShlB protein which also involves conversion of an inactive precursor in an hemolytically active form. Both proteins are synthesized with signal sequences which are released during export across the cytoplasmic membrane. Mutants expressing inactive ShlB derivatives are impaired in activation and secretion suggesting a tight coupling between both processes. The region of ShlA for activation and secretion is confined to the N-terminal 16% of the polypeptide which contains the sequence NPNG which is also found in the Proteus hemolysin, the Bordetella pertussis filamentous hemagglutinin and two highly expressed outer membrane proteins of Haemophilus influenzae. Substitution of the first asparagine (N) residue by isoleucine converts the Serratia hemolysin into an inactive secretion incompetent form. It is concluded that this region is recognized by ShlB for activation and secretion of ShlA. The Serratia hemolysin forms defined pores in erythrocyte membranes.
 ...
PMID:Serratia marcescens forms a new type of cytolysin. 147 65

We have isolated cDNA clones from rat C6 glioma cells coding for several guanine nucleotide-binding regulatory protein (G protein) alpha subunits (G alpha). The cDNA clones were then used to isolate human chromosomal genes. Among human genomic clones isolated by cross-hybridization with the rat cDNA for the alpha subunit of the inhibitory G protein Gi2, termed Gi2 alpha, a clone designated lambda HGi62 was found to contain a sequence that is highly homologous but distinct from any of the known G alpha sequences, and we have tentatively designated this sequence Gx alpha. We have searched a rat brain cDNA library with the Gx alpha sequence and isolated a cDNA clone containing a rat sequence similar to human Gx alpha. The cDNA contained a single open reading frame of 1065 nucleotides coding for a protein of 355 amino acids with a calculated molecular weight of 40,879. The amino acid sequence of rat Gx alpha shows 66% and 40% similarity with rat Gi2 alpha and rat Gs alpha (the alpha subunit of the stimulatory G protein), respectively. By RNA blot hybridization analysis, mRNA of approximately 3.2 kilobases was detected mainly in brain. Interestingly, the deduced amino acid sequence of Gx alpha predicts that the Gx alpha protein may be refractory to modification by pertussis toxin since the cysteine residue in the fourth position from the C terminus of pertussis toxin-sensitive G alpha is replaced by isoleucine.
 ...
PMID:Sequence analysis of cDNA and genomic DNA for a putative pertussis toxin-insensitive guanine nucleotide-binding regulatory protein alpha subunit. 245 69

Hormonally stimulated secretion of ACTH from AtT-20 mouse pituitary tumor cells is a cyclic AMP-mediated process. The presence of inhibitory cholinergic muscarinic receptors on these cells was recently reported, and in this study, the relationship between the activation of these receptors and the consequent inhibition of cyclic AMP formation and ACTH secretion was investigated. The muscarinic agent, oxotremorine, antagonized both cyclic AMP synthesis and ACTH secretion in response to corticotropin-releasing factor (CRF), vasoactive intestinal peptide, a 27-amino acid peptide with an N-terminal histidine and a C-terminal isoleucine amide, and forskolin. Other muscarinic agents, carbachol and bethanechol, had similar inhibitory effects. The cholinomimetics reduced basal (unstimulated) ACTH secretion without decreasing basal cyclic AMP levels, and also antagonized hormone release in response to cyclic AMP-independent agonists such as K+, A-23187, and phorbol ester. Scopolamine reversed the inhibitory effects of the muscarinic agents on basal and stimulated ACTH secretion and cyclic AMP formation. Increasing the extracellular calcium concentration reversed the muscarinic antagonism of basal and CRF-stimulated hormone release without affecting the cyclic AMP response. Pertussis toxin pretreatment attenuated the inhibitory effects of the muscarinic agents on forskolin-stimulated cyclic AMP synthesis and ACTH secretion as well as the inhibitory effect of carbachol on basal ACTH release. The data suggest that cyclic AMP is an essential mediator in the ACTH secretory pathway, but that an alternate cyclic AMP-independent ACTH pathway also exists in the clonal cells, and that both pathways may be modulated by a common postcholinergic receptor mechanism.
 ...
PMID:Inhibition of ACTH secretion in mouse pituitary tumor cells by activation of muscarinic cholinergic receptors. 299 73

The amino acid consumption by Bordetella pertussis growing in broth containing casein hydrolysate was examined. Serine, proline, alanine, glycine, aspartate, and glutamate were rapidly consumed, in a manner which suggested that they supplied the energy requirements of the organism; exhaustion of the energy source appeared to be the main factor limiting the yield of cells. There was no correlation between the utilization of individual amino acids and the phase of growth; uptake appeared to depend only upon relative concentrations. Consumption of threonine, phenylalanine, histidine, leucine, and methionine was slight; consumption of valine and lysine was variable, and isoleucine was excreted. The addition of monosodium l-glutamate (3 mg/ml) to the broth in shaken flasks increased the cell yield by an average of 43.5%. It had no detectable adverse effect upon the agglutin-producing capacity, agglutinability in antisera versus smooth and rough growth phases, mouse-lethal toxicity, histamine-sensitizing factor potency, or intracerebral protective potency of the culture. Broth supplemented with monosodium l-glutamate has been used over a 2-year period to prepare experimental vaccines by both batch and continuous cultivation methods at controlled pH; the cell yields obtained from the supplemented broth have been up to 52% higher than those from the basal broth. The use of glutamate to replace a proportion of casein hydrolysate in the broth caused a reduction in the cell yield, an alteration in cell morphology, and reduction in the mouse-lethal toxicity, the histamine-sensitizing factor potency, and the intracerebral protective potency of the cells.
 ...
PMID:Use of glutamic acid to supplement fluid medium for cultivation of Bordetella pertussis. 431 42

Human tonsillar lymphocytes were cultured in the presence of different activators and [14C]-isoleucine. De novo synthesized, [14C]-labeled immunoglobulin was determined after separation of the different classes by immunoadsorbants carrying class-specific anti-human IgA, IgG, IgM, IgD or IgE. Pokeweed mitogen and whole killed Bordetella pertussis enhanced the synthesis and secretion of IgA, IgG and IgM. Maximum stimulation was found with pokeweed mitogen in IgM secretion (up to 5-fold), while Bordetella pertussis had the largest impact on IgA and IgG (4-5 fold increase). The human milk cell factor (demonstrated by Pittard and Bill., Cell. Immunol. 1979, 42, 437.) in the supernatant of cultured milk cells stimulated selectively the synthesis of IgA (4-fold).
 ...
PMID:Pokeweed mitogen, Bordetella pertussis and breast milk cell factor induce preferentially the synthesis of different immunoglobulin classes. 631 33

Effects of vasoactive intestinal peptide (VIP) on T cell migration are mediated by structurally distinct types I (VIPR1) and II (VIPR2) G protein-associated receptors. The two receptor types were proposed to transduce opposite effects on human T cells, since cytokine-induced chemotaxis of VIPR1-bearing HuT 78 human T cells, in contrast to T cells that express VIPR2, was inhibited by VIP. We studied chemotactic effects of VIP and related agonists with different affinities for VIP- and peptide histidine-isoleucine (PHI)-related receptors. All, VIP, secretin (SEC), a specific ligand for VIPR1, helodermin (HEL), an activator of helodermin-preferring VIPR2, as well as PHI, stimulated chemotaxis into micropore filters of both normal human peripheral blood T and B cells. Involvement of VIPRs was supported by inhibition of VIP-related agonist-induced migration of T and B cells with a VIPR antagonist. Peripheral blood lymphocyte (PBL) chemotaxis to VIP, SEC, HEL and PHI was reduced by inhibition of tyrosine kinase and pertussis or cholera toxin, whereas inhibition of protein kinase C only affected SEC-induced chemotaxis of PBL significantly. VIP-related agonists induced deactivation of migration at high concentrations. Findings in PBL suggest that VIPR1 activation can stimulate normal T and B cell chemotaxis. Different signaling mechanisms may be involved in mediating chemotactic activation of VIPRs and PHIRs, which may allow further exploration of receptor-dependent mechanisms and signaling pathways of VIP as mediator of PBL functions.
 ...
PMID:Similar involvement of VIP receptor type I and type II in lymphocyte chemotaxis. 967 Aug 47

Constitutive activity of the recombinant human 5-hydroxytryptamine(1B) (5-HT(1B)) receptor (RC code 2.1.5HT.01.B) was investigated by mutagenesis of the BBXXB motif (in which B represents a basic residue and X a non-basic residue) located in the C-terminal portion of the third intracellular loop. In contrast with wild-type 5-HT(1B) receptors, three receptor mutants (Thr(313)-->Lys, Thr(313)-->Arg and Thr(313)-->Gln) increased their agonist-independent guanosine 5'-[gamma-[(35)S]thio]triphosphate binding response by 26-41%. This activity represented approx. 30% of the maximal response induced by 5-HT and could be reversed by the inverse agonists methiothepin and 3-(3-dimethylaminopropyl)-4-hydroxy-N-(4-pyridin-4-yl phenyl)-benzenamide (GR 55562). Enhanced agonist-independent and agonist-dependent 5-HT(1B) receptor activation was provided by co-expression of a pertussis toxin-resistant rat G(o)alpha Cys(351)-->Ile protein. The wild-type 5-HT(1B) receptor displayed a doubling in basal activity, whereas a spectrum of enhanced basal activities (313-571%) was observed with a series of diverse amino acid substitutions (isoleucine, glycine, asparagine, alanine, lysine, phenylalanine, glutamine and arginine) at the 5-HT(1B) receptor position 313 in the presence of pertussis toxin (100 ng/ml). Consequently, the constitutive 5-HT(1B) receptor activity can be modulated by the mutation of Thr(313), and displays a graded range between 11% and 59% of maximal 5-HT(1B) receptor activation by 5-HT. No clear pattern is apparent in the framework of traditionally cited amino acid characteristics (i.e. residue size, charge or hydrophobicity) to explain the observed constitutive activities. The various amino acid substitutions that yielded enhanced activity are unlikely to make similar intramolecular interactions within the 5-HT(1B) receptor. It is hypothesized that the positioning of the junction between the third intracellular loop and transmembrane domain VI is altered by mutation of Thr(313) in the BBXXB motif and thereby unmasks G(alpha)-protein interaction points.
 ...
PMID:Activation of constitutive 5-hydroxytryptamine(1B) receptor by a series of mutations in the BBXXB motif: positioning of the third intracellular loop distal junction and its G(o)alpha protein interactions. 1051 Mar 11

1 Fusion proteins were constructed between the human 5-HT(1A) receptor and pertussis toxin-resistant forms of both G(i1)alpha and G(o1)alpha mutated at residue(351) from cysteine to either glycine or isoleucine. Each of these was expressed stably in HEK293 cells. 2 Increasing concentrations of GDP inhibited binding of the agonist [(3)H]-8-OH-DPAT but not the antagonist [(3)H]-MPPF to each construct. 3 The IC(50) for GDP was greater for constructs containing isoleucine at residue(351) of the G proteins compared to those with glycine at this position. 4 The G protein antagonist suramin had similar effects to GDP on the binding of [(3)H]-8-OH-DPAT. 5 The proportion of 5-HT(1A) receptor binding sites detected by [(3)H]-MPPF that displayed high affinity for 8-OH-DPAT was significantly greater when the interacting G protein contained isoleucine rather than glycine at residue(351). 6 The 5-HT(1A) receptor displayed similar avidity of interaction with G(i1)alpha and G(o1)alpha. 7 These results indicate that a higher avidity ternary complex is formed between 8-OH-DPAT, the 5-HT(1A) receptor and G proteins when isoleucine rather than glycine is located at residue(351) of the interacting G protein.
 ...
PMID:Regulation of the avidity of ternary complexes containing the human 5-HT(1A) receptor by mutation of a receptor contact site on the interacting G protein alpha subunit. 1223 54

Pertussis toxin (PTX)-insensitive mutants of Galpha(i/o) proteins expressed in C6mu cells were used to examine the hypothesis that there are agonist-specific conformational states of the mu-opioid receptor with coupling preferences to different Galpha(i/o) subtypes, as measured by the degree of stimulation of [(35)S]guanosine 5'-O-(3-thio)triphosphate (GTPgammaS) binding. Binding of [(35)S]GTPgammaS to endogenous Galpha(i/o) proteins stimulated by the full mu-opioid agonist [d-Ala(2),MePhe(4),Gly(5)-ol]enkephalin (DAMGO) was completely blocked by overnight treatment with 100 ng/ml PTX. Treatment for 4 h with lower concentrations led to a PTX-dependent reduction in the maximal effect of DAMGO but no alteration in the potency of DAMGO or morphine nor in the relative maximal effect (relative efficacy) of the partial agonists morphine and buprenorphine compared with the full agonist DAMGO. Using PTX-insensitive Galpha mutants in which the PTX-sensitive cysteine was replaced with isoleucine, the potency for a series of mu-opioid agonists was highest in cells expressing Galpha(i3) and Galpha(o) and lowest with Galpha(i1) and Galpha(i2), with no significant change in the order of potency, namely, etorphine >> endomorphin-1 = DAMGO = endomorphin-2 = fentanyl = morphine >> meperidine. The order of agonist relative efficacy, etorphine = DAMGO = endomorphin-1 = endomorphin-2 = fentanyl > or = morphine > or = meperidine > buprenorphine > or = nalbuphine, was also the same across all of the PTX-insensitive Galpha(i/o) subtypes. Highest relative efficacy to stimulate [(35)S]GTPgammaS binding was seen with Galpha(i3). Consequently, reported observations of agonist-directed trafficking at mu-opioid receptors most likely involve non-PTX-sensitive Galpha protein mechanisms.
 ...
PMID:Comparison of the relative efficacy and potency of mu-opioid agonists to activate Galpha(i/o) proteins containing a pertussis toxin-insensitive mutation. 1643 99

Chronic activation of mu-opioid receptors, which couple to pertussis toxin-sensitive Galphai/o proteins to inhibit adenylyl cyclase (AC), leads to a compensatory sensitization of AC. Pertussis toxin-insensitive mutations of Galphai/o subtypes, in which the pertussis toxin-sensitive cysteine is mutated to isoleucine (Galpha ), were used to determine whether each of the Galphai/o subtypes is able to mediate sensitization of AC. Galpha , G , G or G were individually transiently transfected into C6 glioma cells stably expressing the mu-opioid receptor, or transiently co-expressed with the mu-opioid receptor into human embryonic kidney (HEK)293T cells. Cells were treated with pertussis toxin to uncouple endogenous Galphai/o proteins, followed by acute or chronic treatment with the mu-opioid agonist, [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO). Each Galphai/o subtype mediated acute DAMGO inhibition of AC and DAMGO-induced sensitization of AC. The potency for DAMGO to stimulate sensitization was independent of the Galphai/o subtype, but the level of sensitization was increased in clones expressing higher levels of Galphai/o subunits. Sensitization of AC mediated by a component of fetal bovine serum, which was also dependent on the level of functional Galphai/o subunits in the cell, was observed. This serum-mediated sensitization partially masked mu-opioid-mediated sensitization when expressed as percentage overshoot due to an apparent increase in AC activity.
 ...
PMID:Mediation of adenylyl cyclase sensitization by PTX-insensitive GalphaoA, Galphai1, Galphai2 or Galphai3. 1723 Jun 39


1