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)

To identify the role of ras oncogene and p21 in the coupling mechanism of GTP-binding proteins to adenylate cyclase, we used v-Ki-ras transformed NIH/3T3 fibroblast cells. In the previous study, we investigated that NaF, cholera toxin and forskolin remarkably enhanced the adenylate cyclase activity in transformed cells compared to normal NIH/3T3 cells. In the present study, adenylate cyclase was more enhanced by GTP gamma S in transformed cells than in normal cells. It was considered that p21 plays enhancing role in coupling of GTP-binding proteins to adenylate cyclase. Further, as measured by the degree of [32P] ADP-ribosylation of GTP-binding proteins by cholera toxin and pertussis toxin respectively, the amount of Gs (46 kDa) was almost equal in both cells, while the amount of Gi (41 kDa) in transformant was about one third of that in normal cells. This difference seems to be reflected in either the biological situations or the quantities of Gi. Our data suggest that v-Ki-ras transformation resulted in the decrease of Gi protein so that the inhibitory regulation on adenylate cyclase relatively becomes low and then stimulatory influence of Gs seems to be enhanced.
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PMID:GTP-binding proteins and adenylate cyclase activity in v-Ki-ras transformed NIH/3T3 fibroblast cells. 313 19

GTP-binding proteins were purified from human neutrophils, including a 40,000-Da pertussis toxin substrate (Gn) and 22,000-, 24,000-, and 26,000-Da proteins, termed G22K, G24K, and G26K, respectively. The latter proteins were shown to be immunologically unrelated to Gn. G22K cross-reacted with anti-ras monoclonal antibody 142-24EO5, but not with monoclonal antibody Y13-259. A single 22,000-Da substrate for botulinum toxin-catalyzed ADP-ribosylation present in neutrophil membranes co-migrated upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis with G22K. In the presence of a cytosolic factor, G22K could serve as a specific botulinum toxin substrate. The 22,000-Da botulinum toxin substrate in neutrophil membranes could be immunoprecipitated by antibody 142-24EO5, but not by antibody Y13-259. G22K appears to be a unique GTP-binding protein which serves as a substrate for ADP-ribosylation by a component of botulinum toxin and which may be involved in exocytotic secretion or cellular differentiation.
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PMID:Purification and characterization of the 22,000-dalton GTP-binding protein substrate for ADP-ribosylation by botulinum toxin, G22K. 314 12

Microinjection of monoclonal antibodies (lines 238, 172, and 259) directed against the ras gene product, p21, into Xenopus laevis oocytes accelerated progesterone-induced germinal vesicle breakdown. Antibody 238 had the greatest effect on the acceleration of progesterone-induced oocyte maturation, and this effect was correlated with in vitro inhibition of adenylate cyclase (EC 4.6.1.1) activity in a concentration-dependent manner. Inhibition of adenylate cyclase by antibody 238 was also measured in membranes prepared from oocytes pretreated with either cholera toxin or pertussis toxin. These results suggest a role for the ras gene product in the regulation of vertebrate cell adenylate cyclase activity.
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PMID:Antibodies to the ras gene product inhibit adenylate cyclase and accelerate progesterone-induced cell division in Xenopus laevis oocytes. 353 92

A bovine retinal complementary DNA clone encoding the alpha subunit of transducin (T alpha) was isolated with the use of synthetic oligodeoxynucleotides as probes, and the complete nucleotide sequence of the insert was determined. THe predicted protein sequence of 354 amino acids includes the known sequences of four tryptic peptides and sequences adjacent to the residues that undergo adenosine diphosphate ribosylation by cholera toxin and pertussis toxin. On the basis of homologies to other proteins, such as the elongation factors of protein synthesis and the ras oncogene proteins, regions are identified that are predicted to be acylated and involved in guanine nucleotide binding and hydrolysis. Amino acid sequence similarity between T alpha and ras is confined to these regions of the molecules.
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PMID:Sequence of the alpha subunit of photoreceptor G protein: homologies between transducin, ras, and elongation factors. 385 23

SH-PTP1 is a protein tyrosine phosphatase (PTP) predominantly expressed in haematopoietic cells and containing two src homology-2 (SH2) domains. Here we report that SH-PTP1 is phosphorylated on both serine and tyrosine residues in response to thrombin or phorbol myristate acetate (PMA), which increased by 60 and 40%, respectively, SH-PTP1 activity. Thrombin-induced phosphorylation of SH-PTP1 is an early signalling event (maximal within 10 s) involving neither integrin signalling, nor calcium, nor release of ADP or thromboxane A2. Moreover, in contrast with PMA, the effect of thrombin on the tyrosine phosphorylation of SH-PTP1 was hardly affected by GF109203X, a specific protein kinase C (PKC) inhibitor. Finally, phosphorylation of SH-PTP1 could be provoked in permeabilized platelets by thrombin or GTP gamma S. This was abolished by pertussis toxin, the specificity of this effect being verified with the megakaryocytic cell line Dami cell. Our data thus identify SH-PTP1 as an in vivo substrate of a putative protein tyrosine kinase linked to the thrombin receptor by a Gi protein. This might offer some clue to unravel the mechanism of thrombin not only in platelets but also in nucleated cells, where its mitogenic effect is known to involve pertussis toxin-sensitive G-proteins, tyrosine phosphorylation and the ras pathway.
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PMID:Tyrosine phosphorylation of an SH2-containing protein tyrosine phosphatase is coupled to platelet thrombin receptor via a pertussis toxin-sensitive heterotrimeric G-protein. 778 4

Lysophosphatidylinositol has been previously shown to stimulate cell proliferation in differentiated and in K-ras transformed thyroid cells. Increased levels of lysophosphatidylinositol, but not lysophosphatidylcholine or lysophosphatidylethanolamine, are present in thyroid as well as in other ras-transformed cell lines. We have now investigated the mechanism of action of this lysolipid by analysing its effects in a differentiated thyroid cell line. Lysophosphatidylinositol did not increase the levels of cAMP, the main stimulator of cell proliferation in the thyroid, whereas it stimulated phosphoinositide breakdown, mobilization of cytosolic Ca2+ and arachidonic acid release, suggesting that it activates both phospholipases C and A2. None of the effects of lysophosphatidylinositol were prevented by pretreatment of cells with pertussis toxin. Instead, the tyrosine kinase inhibitors, tyrphostins AG18 and AG561, completely blocked its mitogenic action. The effects of lysophosphatidylinositol were distinguishable from those of the well known mitogen lysophosphatidic acid, which affected differently the signalling pathways analysed and was not mitogenic in ras-transformed cells. These results suggest that the mitogenic activity of lysophosphatidylinositol is associated with the activation of phospholipase C and phospholipase A2 and is relatively specific for ras-transformed cells.
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PMID:Signalling pathways involved in the mitogenic action of lysophosphatidylinositol. 778 56

Significant amounts of leukotriene B4 (LTB4) are generated by human polymorphonuclear neutrophils (PMNs) after incubation with the Panton-Valentine leukocidin (Luk-PV) from Staphylococcus aureus V8 strains. We showed that GTP-binding proteins (G proteins) are involved in the Luk-PV-activated signal transduction of PMNs. ADP-ribosylation of heterotrimeric G proteins by cholera and pertussis toxins decreased the Luk-PV-induced LTB4-generation. In contrast, ADP-ribosylation of the low-molecular-weight G proteins rho and rac by Clostridium botulinum exoenzyme C3 increased the Luk-PV-induced LTB4 synthesis. The subsequent stimulation of Luk-PV-treated PMNs by either calcium ionophore A23187, sodium fluoride, or formylmethionyl-leucyl-phenylalanine was significantly inhibited. This decrease was paralleled by a loss of G-protein functions, including GTPase activity and GTP-binding capacity. An increase of G-protein functions was obtained with low amounts of Luk-PV. In addition to the modulated G-protein functions, ADP-ribosylation of 24-, 40-, and 45-kDa proteins by Luk-PV was detected. As shown in control experiments, the ADP-ribosylated 24-kDa proteins were not substrates for C. botulinum exoenzyme C3. Introduction of ras p21 into digitonin-permeabilized PMNs was without effect on subsequent Luk-PV stimulation. In addition, the translocation of ras p21, ras GAP, and 5-lipoxygenase into the membrane of Luk-PV-treated PMNs, as well as the expression of chemotactic membrane receptors for LTB4 and formylmethionyl leucyl phenylalanine, was significantly diminished.
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PMID:GTP-binding proteins are involved in the modulated activity of human neutrophils treated with the Panton-Valentine leukocidin from Staphylococcus aureus. 796 Jan 6

The nature of GTP-binding components associated with isolated human term placental syncytiotrophoblast microvillous plasma membrane vesicles (SPMV) was determined; these are relevant to elucidation of intracellular signal transduction mechanisms. Four proteins were identified, with molecular weights of 29, 27, 23 and 21 kDa, which specifically bound [alpha-32P]GTP in the presence of Mg2+. Studies employing anti-p21c-ras monoclonal antibodies indicated these four GTP-binding components were ras-related and one, the 21 kDa component, may be p21c-ras. In addition, SPMV were also found to express the alpha subunits of three separate G proteins. A 45 kDa SPMV GTP-binding protein was identified as a substrate for Vibrio cholera toxin and was recognized by a rabbit antibody to the alpha subunit of the adenylate cyclase stimulating G protein, Gs. A 41 kDa SPMV GTP-binding protein substrate of Bordetella pertussis toxin was also recognized by rabbit antibodies to the alpha subunits of the adenylate cyclase inhibiting G proteins, Gi-1 and Gi-3. No evidence was found to support the presence of the 21 kDa Gp, a G protein previously associated with membranes prepared from whole placental tissue homogenates.
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PMID:GTP-binding proteins associated with the human placental syncytiotrophoblast plasma membrane. 820 66

Direct photoaffinity labeling of proteins of longitudinal sarcoplasmic reticulum (LSR) of rabbit skeletal muscle with [32P]GTP revealed GTP-binding proteins of about 52, 45 and 30 kDa. ADP-ribosylation with [32P]NAD in the presence of cholera toxin (CTX) or pertussis toxin (PTX) indicates the existence of a CTX substrate (about 45 kDa); no PTX substrates were observed. Western blots of LSR probed with RM/1, an antiserum against a decapeptide from the C-terminus of Gs alpha, showed an immunoreactive band at about 45 kDa. [32P]GTP overlays of Western blots of LSR showed a heavily-labeled protein of about 29 kDa and one or more additional slightly smaller proteins that were more weakly labeled. When LSR was subjected to mild trypsin hydrolysis, the Western blot overlay revealed three bands at about 23, 25 and 29 kDa. Western blots of LSR proteins showed no significant immunoreactivity with the anti-(pan)-ras monoclonal antibodies 142-24E05 and Ras 11. ADP-ribosylation of LSR with [32P]NAD in the presence of C3 exoenzyme of Clostridium botulinum yielded a labeled band at about 23 kDa. Our results indicate the presence in rabbit LSR of a Gs alpha, the absence of Gi and G(o), and the presence of several low molecular weight GTP-binding proteins, distinct from p21 ras, one of which belongs to the rho or rac family.
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PMID:Identification of heterotrimeric and low molecular weight GTP-binding proteins in rabbit skeletal muscle longitudinal sarcoplasmic reticulum. 841 93

In cultured rat vascular smooth muscle cells, angiotensin II (Ang II) induced a rapid increase in mitogen-activated protein kinase (MAPK) activity through the Ang II type 1 receptor, which was insensitive to pertussis toxin but was abolished by the phospholipase C inhibitor, U73122. The Ang II-induced MAPK activation was not affected by the protein kinase C inhibitor, GF109203X, and was only partially impaired by pretreatment with a phorbol ester, whereas both treatments completely prevented MAPK activation by the phorbol ester. Intracellular Ca2+ chelation by TMB-8, but not extracellular Ca2+ chelation or inhibition of Ca2+ influx, abolished Ang II-induced MAPK activation. The calmodulin inhibitor, calmidazolium, and the tyrosine kinase inhibitor, genistein, completely blocked MAPK activation by Ang II as well as by the Ca2+ ionophore A23187. Ang II caused a rapid increase in the binding of GTP to p21(ras), and this was inhibited by genistein, TMB-8, and calmidazolium but not by pertussis toxin or GF109203X. These data suggest that Ang II-induced MAPK activation through the Ang II type 1 receptor could be mediated by p21(ras)activation through a currently unidentified tyrosine kinase that lies downstream of Gq-coupled Ca2+/calmodulin signals.
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PMID:Identification of an essential signaling cascade for mitogen-activated protein kinase activation by angiotensin II in cultured rat vascular smooth muscle cells. Possible requirement of Gq-mediated p21ras activation coupled to a Ca2+/calmodulin-sensitive tyrosine kinase. 866 12


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