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)

NIH-3T3 cells transformed by the EJ-ras oncogene display reduced platelet-derived growth factor (PDGF)-stimulated phospholipase C activity as measured by inositol 1,4,5-triphosphate (IP3) synthesis and Ca2+ mobilization. The lack of PDGF-stimulated Ca2+ mobilization in EJ-ras transformed cells is not due to a loss of IP3 sensitivity, because microinjected IP3 elevates intracellular Ca2+. Treatment of EJ-ras transformed cells with cholera toxin or 8-bromo-cyclic AMP, but not pertussis toxin or the beta-subunit of cholera toxin, results in a slight recovery of PDGF-stimulated IP3 synthesis, a marked increase in intracellular Ca2+ mobilization, and an almost complete recovery of prostaglandin E2 biosynthesis. These data suggest that EJ p21-mediated inhibition of PDGF-stimulated intracellular events can be partially and transiently reversed by cyclic AMP.
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PMID:Cyclic AMP can partially restore platelet-derived growth factor-stimulated prostaglandin E2 biosynthesis, and calcium mobilization in EJ-ras-transformed NIH-3T3 cells. 254 Nov 40

Stable expression of high levels of activated forms of Haras (T24) or v-Ki-ras by transfection of Chinese hamster lung fibroblasts (CCL39) yielded cells highly tumorigenic in nude mice. Two classes of transformed cells were distinguished, one with moderate p21 expression (10-fold increased) had retained growth factor dependency, the second with higher level of p21 (greater than 50-fold) appeared autonomous for growth. Neither class of transformants expressing Ki-ras or Ha-ras displayed a significant basal activity of polyphosphoinositide-specific phospholipase C, measured either in serum-starved cells or during exponential growth in the presence of growth factors of the tyrosine kinase family (EGF, FGF, insulin). In the growth-factor-dependent class of T24-Ha-ras-transfected cells (clone 39THaB), phospholipase C could be stimulated normally by serum, thrombin and AlF-4. In the more growth autonomous class (clones 39THaC and 39Ki9), release of inositol phosphates after stimulation with thrombin or serum was drastically reduced. This desensitization, apparently at the receptor level since the response to AlF-4 persisted, is, however, not specific to ras expression. We observed it to the same degree in polyoma virus-transformed CCL39 cells. Finally, expression of mutated forms of p21 ras did not abrogate the sensitivity of phospholipase C activation to pertussis toxin. We conclude that the transforming potential of activated forms of p21ras does not result from persistent activation of phospholipase C and that ras GTP-binding proteins cannot substitute for Gp.
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PMID:Deregulation of hamster fibroblast proliferation by mutated ras oncogenes is not mediated by constitutive activation of phosphoinositide-specific phospholipase C. 283

The role of ras-encoded proteins and platelet-derived growth factor (PDGF) in inositol phospholipid metabolism has been studied. PDGF stimulates inositol phospholipid turnover in confluent normal rat kidney (NRK) cells and enhances hydrolysis of phosphatidylinositol monophosphate and phosphatidylinositol bisphosphate in NRK cell membranes in the presence of guanosine 5'-[gamma-thio]triphosphate. The stimulatory effect of PDGF on phosphatidylinositol bisphosphate hydrolysis is not inhibited by pretreatment of NRK cells with pertussis toxin, implying that PDGF-stimulated phospholipase C activity of NRK cells is regulated by a pertussis toxin-insensitive guanine nucleotide-binding protein (G protein) that is different from Gi (inhibitory G protein) or Go (G protein of unknown function). When bacterially made human normal or oncogenic T24 ras protein is added to 32P-labeled NRK cell membranes in the presence of guanosine 5'-[gamma-thio]triphosphate, normal ras protein increases by 3-fold the formation of inositol trisphosphate, whereas T24 ras protein has no significant effect. In addition, normal ras protein and PDGF have additive effects on inositol trisphosphate production. Taken together, these data suggest that normal ras protein stimulates inositol phospholipid turnover in NRK cells by means of a pathway different from the PDGF-regulated one and that oncogenic ras protein is without significant stimulatory effect in this action.
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PMID:Effects of ras-encoded proteins and platelet-derived growth factor on inositol phospholipid turnover in NRK cells. 284 49

The sequence of the 350 amino acids in the alpha subunit of GTPase of bovine rod outer segments has been determined. Enriched GTPase mRNA was used to prepare a cDNA library in the expression vector lambda gt11 and several overlapping cDNA clones corresponding to the alpha subunit of the GTPase were identified. The cDNA sequence determined contains 93 nucleotides upstream of the 5' end of the coding region, 1050 nucleotides that specify the amino acid sequence, and 45 nucleotides downstream from the 3' end. The previously described partial amino acid sequences and the sequences at the ADP-ribosylation sites for cholera and pertussis toxins are all confirmed and fitted into the present complete sequence. Homologies are found between the sequence of the alpha subunit and those of other guanine nucleotide-binding proteins, the ras proteins, peptide chain elongation factors EF-Tu and EF-G, and the initiation factor IF2.
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PMID:GTPase of bovine rod outer segments: the amino acid sequence of the alpha subunit as derived from the cDNA sequence. 298 13

Recent studies have shown that the 21-kilodalton protein (p21) Ha-ras gene product shares sequence homology with and may exhibit biochemical properties similar to the mammalian guanine nucleotide-binding proteins. These data suggested that one of the biochemical functions of p21 in the vertebrate cell may be to regulate adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1]. We determined both in intact NIH-3T3 murine cells and in membranes isolated from these cells that the hormone-stimulated adenylate cyclase activity of cells expressing the EJ human bladder carcinoma oncogene (EJ-ras) is significantly reduced compared with control cells. Thus, the levels of cAMP measured in the EJ-ras-transformed cells by radioimmunoassay are reduced 78% and 93% after prostaglandin and isoproterenol stimulation, respectively, compared with the levels in control cells. Treatment of the EJ-ras-transformed cells with pertussis toxin or cholera toxin did not correct the alterations in adenylate cyclase activity. Cells expressing the normal human Ha-ras gene displayed intermediate levels of adenylate cyclase hormone sensitivity; these levels of adenylate cyclase activity were greater than those in the EJ-ras-transformed cells but lower than in control cells. Hormone-stimulated adenylate cyclase activities in cells transfected with Rous sarcoma virus DNA were similar to those in control cells. These data support the hypothesis that both the normal and mutated Ha-ras p21s are related to guanine nucleotide-binding proteins.
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PMID:Reduced hormone-stimulated adenylate cyclase activity in NIH-3T3 cells expressing the EJ human bladder ras oncogene. 301 29

Pertussis toxin (PT), which blocks the activity of several G-proteins, has been found to exert a marked inhibitory effect on the DNA synthesis induced in 3T3 cells by serum or growth factors. 3T3 cells transformed with human c-ras oncogenes (Ha-ras, Ki-ras, N-ras) or with src, an oncogene coding for a protein kinase, have lost sensitivity to growth control by PT, even though substrates for PT can still be ADP-ribosylated in vivo. In contrast, 3T3 cells transformed with the SV40 virus behave like normal untransformed cells with respect to the ability of PT to decrease their growth rate. Oncogenes can thus likely be classified either as 'responders' or 'non-responders' to PT.
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PMID:Differential sensitivity to pertussis toxin of 3T3 cells transformed with different oncogenes. 304 49

A bovine retinal cDNA clone encoding the complete sequence (354 amino acids) of Go alpha, a guanine nucleotide-binding protein (G protein), was isolated by using oligonucleotide probes complementary to published sequences in two putative clones for the alpha subunit of bovine transducin (T alpha). The deduced amino acid sequence contained sequences identical to those in seven tryptic peptides (total 63 amino acids) from bovine brain Go alpha. The cDNA for bovine retinal Go alpha exhibits greater than 90% identity in both coding and 3' untranslated regions with a recently described partial cDNA clone for Go alpha from rat brain [Itoh, H., Kozasa, T., Nagata, S., Nakamura, S., Katada, T., Ui, M., Iwai, S., Ohtsuka, E., Kawasaki, H., Suzuki, K. & Kaziro, Y. (1986) Proc. Natl. Acad. Sci. USA 83, 3776-3780]. Comparison of the nucleotide and deduced amino acid sequences of the bovine Go alpha clone with those previously reported for other G proteins of bovine origin (Gs alpha, Gi alpha, and T alpha) reveals extensive regions identical to those surrounding the amino acids modified by cholera toxin and pertussis toxin. There are also marked similarities of sequence in regions of the G proteins, elongation factors, and the ras p21 gene products that are believed to be involved in guanine nucleotide binding and GTP hydrolysis.
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PMID:Deduced amino acid sequence of bovine retinal Go alpha: similarities to other guanine nucleotide-binding proteins. 310 61

One of the major steps in the understanding of the hormonal and sensory transduction mechanisms in eukaryotic cells has been the discovery of a family of GTP binding proteins which couple receptors to specific cellular effectors. The absolute requirement of GTP for hormonal stimulation of adenylate cyclase was the initial observation which led to the purification of the protein involved: Gs. Gs couples stimulatory receptors to adenylate cyclase. It is a heterotrimer composed of an alpha chain (45 or 52 kDa), a beta chain (35-36 kDa) and a gamma chain (8 kDa). Several other G proteins of known functions have been purified: Gi, which couples inhibitory receptors to adenylate cyclase, and transducin which couples photoexcited rhodopsin to cyclic GMP phosphodiesterase. Some G proteins of uncertain function have also been purified: Go, a G protein mainly localized in nervous tissues and Gp, a G protein isolated from placenta and platelets. All these G proteins have a common design. Like Gs they all consist of 3 chains: alpha, beta and gamma. The beta chains are nearly identical, whereas the gamma chains are more variable. The alpha chains are different, but share common domains (especially at the level of the GTP binding site). These domains of homologies are also similar to those of other GTP binding proteins, such as the product of the ras gene (p21) and the initiation or elongation factors. alpha Chains are also ADP ribosylated by bacterial toxins. Gs and transducin are targets for cholera toxin, whereas Gi, Go and transducin are targets for pertussis toxin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:GTP binding proteins: a key role in cellular communication. 311 13

We describe here the existence of previously undescribed GTP-binding proteins within the human neutrophil. These proteins specifically bind guanine nucleotides under conditions in which the previously characterized G-proteins are unable to bind. We have partially purified these proteins and present both functional and immunologic data which indicate that they are unrelated to Gn, the major neutrophil pertussis toxin substrate. An additional protein, of apparent molecular mass 22 kDa, may be related to the ras G-protein family. Analysis of the structural and functional characteristics of these novel proteins will promote a better understanding of the process of neutrophil activation.
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PMID:Identification of novel GTP-binding proteins in the human neutrophil. 312 73

The regulation of adenylate cyclase has been analyzed in normal rat thyroid cells as well as in the same cells transformed by the v-ras-k oncogene. In both cell types the adenylate cyclase complex consists of the two GTP-binding proteins, Gi and Gs, as demonstrated by the specific ADP-ribosylation induced by pertussis and cholera toxin, respectively. The response of adenylate cyclase of the transformed cells to forskolin, pertussis toxin and cholera toxin is attenuated with respect to the control cell line. The thyrotropic hormone (TSH), that acts on normal thyroid cells in culture as a growth factor by stimulating the adenylate cyclase activity, is not able to induce DNA synthesis nor does it stimulate adenylate cyclase in v-ras-k transformed cells.
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PMID:Adenylate cyclase activity of v-ras-k transformed rat epithelial thyroid cells. 312 65


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