Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The possibility, that a GTP-binding protein is involved in the transducing mechanism leading to the formation of inositol trisphosphate (InsP3) in heart was explored in rat heart ventricles. Accordingly, a crude membrane fraction was isolated from 3[H] inositol prelabelled rat heart ventricles. When incubated with the non-hydrolysable GTP analogues GTP gamma S and GMP-PNP, it produced InsP3 in a time- and concentration-dependent manner. GDP beta S and the aminoglycoside antibiotic neomycin were effective inhibitors of this activation. In the absence of GTP gamma S or GMP-PNP, no such formation occurred with Ca2+ concentration from 10 nM to 1 microM but formation tripled in relation to the control level when Ca2+ concentration was raised from 1 microM to 100 microM. GTP gamma S increased the Ca2+ sensitivity of InsP3 production towards more physiologically relevant concentrations occurring during diastole (100 nM). These findings strongly suggest the presence in heart of a particulate Ca2(+)-dependent phospholipase C, whose activity is regulated by guanine nucleotides. This Ca2(+)-dependent phospholipase C observed in a cell free system was evidenced also in a multicellular system when altering the free Ca2+ concentrations around the physiological range. The results support the possibility that the enzyme might be activated during each cardiac cycle and thus produce two potential activators of cardiac contraction, namely InsP3 and diglycerides.
J Mol Cell Cardiol 1990 Jan
PMID:Mediation by GTP gamma S and Ca2+ of inositol trisphosphate generation in rat heart membranes. 218 85

A new lipophilic immunomodulator, disaccharide tripeptide glycerol dipalmitoyl (DTP-GDP), has been synthesized and evaluated for its immunologic activity and toxicology. DTP-GDP alone or in liposomes is more effective as an adjuvant and in activating macrophages compared with muramyldipeptide (MDP). Preclinical studies demonstrate no evidence of toxicity, including vasculitis. DTP-GDP in liposomes has shown antitumor activity in phase I clinical trials.
Mol Biother 1990 Mar
PMID:Immunologic and toxicologic study of disaccharide tripeptide glycerol dipalmitoyl: a new lipophilic immunomodulator. 218 94

The effect of ketoconazole on the fusion of L6 myoblasts was studied. Ketoconazole was a potent inhibitor of myoblast fusion at concentrations as low as 0.1 microM, but fusion was restored when the inhibitor was removed. The inhibitor resulted in decreased binding of conA and WGA to cell surface oligosaccharides showing that it was inhibiting N-linked cell surface glycoproteins. Inhibition of fusion by ketoconazole was accompanied by reduced creatine phosphokinase activities showing that it is affecting biochemical differentiation. Incorporation of labelled mannose from GDP-mannose into lipid-sugar and lipid-oligosaccharide complexes involved in the synthesis of N-linked oligosaccharides was also inhibited by ketoconazole, but the inhibition was reversed by addition of exogenous dolichol phosphate to the incorporation mixture. The main conclusion from these studies was that ketoconazole inhibited fusion of L6 myoblasts by affecting the synthesis of dolichol-phosphate required for the synthesis of lipid-oligosaccharides needed for the synthesis of fusogenic cell surface N-linked glycoproteins.
Mol Cell Biochem 1990 Feb 09
PMID:Studies on the effect of ketoconazole on the fusion of L6 myoblasts. 230 83

Transfer RNA protects a characteristic set of bases in 16 S rRNA from chemical probes when it binds to ribosomes. We used several criteria, based on construction of well-characterized in vitro ribosome-tRNA complexes, to assign these proteins to A or P-site binding. All of these approaches lead to similar conclusions. In the A site, tRNA caused protection of G529, G530, A1492 and A1493 (strongly), and A1408 and G1494 (weakly). In the P site, the protected bases are G693, A794, C795, G926 and G1401 (strong), and A532, G966, G1338 and G1339 (weak). In contrast to what is observed for 23 S rRNA, blocking the release of EF-Tu.GDP from the ribosome by kirromycin has no detectable effect on the protection of bases in 16 S rRNA.
J Mol Biol 1990 Jan 05
PMID:Binding of tRNA to the ribosomal A and P sites protects two distinct sets of nucleotides in 16 S rRNA. 240 62

High affinity binding of guanine nucleotides and the ability to hydrolyze bound GTP to GDP are characteristics of an extended family of intracellular proteins. Subsets of this family include cytosolic initiation and elongation factors involved in protein synthesis, and cytoskeletal proteins such as tubulin (Hughes, S.M. (1983) FEBS Lett. 164, 1-8). A distinct subset of guanine nucleotide binding proteins is membrane-associated; members of this subset include the ras gene products (Ellis, R.W. et al. (1981) Nature 292, 506-511) and the heterotrimeric G-proteins (also termed N-proteins) (Gilman, A.G. (1984) Cell 36, 577-579). Substantial evidence indicates that G-proteins act as signal transducers by coupling receptors (R) to effectors (E). A similar function has been suggested but not proven for the ras gene products. Known G-proteins include Gs and Gi, the G-proteins associated with stimulation and inhibition, respectively, of adenylate cyclase; transducin (TD), the G-protein coupling rhodopsin to cGMP phosphodiesterase in rod photoreceptors (Bitensky, M.W. et al. (1981) Curr. Top. Membr. Transp. 15, 237-271; Stryer, L. (1986) Annu. Rev. Neurosci. 9, 87-119), and Go, a G-protein of unknown function that is highly abundant in brain (Sternweis, P.C. and Robishaw, J.D. (1984) J. Biol. Chem. 259, 13806-13813; Neer, E.J. et al. (1984) J. Biol. Chem. 259, 14222-14229). G-proteins also participate in other signal transduction pathways, notably that involving phosphoinositide breakdown. In this review, I highlight recent progress in our understanding of the structure, function, and diversity of G-proteins.
Mol Cell Endocrinol 1987 Jan
PMID:Signal transduction by guanine nucleotide binding proteins. 243 86

The neutralizing monoclonal antibody Y13-259 severely hampers the nucleotide exchange reaction between p21-bound and exogenous guanine nucleotides but does not interfere with the association of GDP to p21. These results suggest that the nucleotide exchange reaction is critical for p21 function. Interestingly, the v-ras p21 has a much faster dissociation rate than the p21 of the c-ras proto-oncogene.
Mol Cell Biol 1987 May
PMID:Neutralizing monoclonal antibody against ras oncogene product p21 which impairs guanine nucleotide exchange. 243 1

A new GTP-binding protein, which serves as a substrate for pertussis toxin, was prepared from porcine brain. The new G protein was separated from other GTP-binding proteins, Gi and Go, by an anion-exchange column chromatography. The mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the alpha subunit of the new G protein was between those of alpha subunits of Gi and Go. Evidence that the alpha subunit is not a proteolytic fragment of the alpha subunit is not a proteolytic fragment of the alpha subunit of Gi or Go was provided by experiments involving partial hydrolysis of these G proteins with thermolysin and their interaction with an antibody raised against the amino terminal peptide of the alpha subunit of Gi. In addition, the gamma subunit of the new G protein was indicated to be different from the gamma subunits of Gi and Go, because the latter were found to be phosphorylated by protein kinase C but the former was not. GTP-sensitive high affinity binding of muscarinic receptors with acetylcholine was observed when muscarinic receptors purified from porcine cerebrum were reconstituted in phospholipid vesicles with the new G protein as well as with Gi or Go. The proportion of the high affinity sites increased with the concentrations of the G proteins, the potency of the new G protein being similar to that of Gi but a little lower than that of Go. This GTP-sensitive high affinity binding was not observed when each G protein was pretreated with pertussis toxin and then reconstituted with muscarinic receptors. Acetylcholine accelerated the dissociation of [3H]GDP from the new G protein as well as from Gi and Go, which were reconstituted with muscarinic receptors. These results indicate that muscarinic receptors interact with at least the above three kinds of G proteins, in a pertussis toxin-sensitive manner.
Mol Pharmacol 1989 Mar
PMID:Cerebral muscarinic acetylcholine receptors interact with three kinds of GTP-binding proteins in a reconstitution system of purified components. 249 27

We have previously reported incorporation of Triton X-100-solubilized bovine calf testis membrane protein into liposomes. The resulting proteoliposomes responded to FSH by exchange of bound GDP for [3H]5'-guanylyl imidodiphosphate ([3H]Gpp(NH)p) and by activation of adenylate cyclase (AC) (Grasso, P., Dattatreyamurty, B. and Reichert, L.E., Jr. (1988) Mol. Endocrinol. 2, 420-430). This model system was utilized to study the effects of FSH on the quaternary structure of FSH receptor-associated GTP-binding protein by comparing the gel filtration profiles of proteoliposomes solubilized with Triton X-100 after exposure to [3H]Gpp(NH)p in the presence or absence of FSH. FSH caused a redistribution of radioactivity (due to bound [3H]Gpp(NH)p) from a high molecular weight fraction (Mr greater than 100,000) to a fraction of much lower molecular weight (Mr approximately 23,000). These results are interpreted to reflect an FSH-induced dissociation of [3H]Gpp(NH)p-bound G protein from its receptor-associated complex. The apparent Mr of approximately 23,000 for the FSH receptor-associated GTP-binding protein suggests that it may represent yet another member of a family of low molecular weight GTP-binding proteins, possibly a ras gene product, recently identified in various mammalian tissues.
 ...
PMID:Follicle stimulating hormone (FSH) induces G protein dissociation from FSH receptor-G protein complexes in reconstituted proteoliposomes. 250 56

In intact membranes as well as after reconstitution into phospholipid vesicles, pertussis toxin (PT)-mediated ADP-ribosylation of G proteins causes loss of receptor-mediated regulation of effectors and/or G protein-mediated regulation of receptor binding. Studies were carried out to test which of several discrete steps known to constitute the basal and receptor-stimulated regulatory cycles of Gi proteins are affected by PT. Experiments with the Gs-deficient Gi-regulated adenylyl cyclase of cyc- S49 cell membranes indicated that PT blocks Gi activation by GTP without affecting GDP dissociation or GTP binding to a major extent. This suggested that the block lies in the transition of inactive GTP-Gi to active GTP-Gi (G to G* transition). Experiments with purified Gi in solution and after incorporation into phospholipid vesicles showed that PT does not increase or decrease the intrinsic GTPase activity of Gi. Experiments in which Gi was incorporated into phospholipid vesicles with rhodopsin, a receptor that interacts with Gi to stimulate the rate of guanosine 5'-O-(3-thio)triphosphate binding and GTP hydrolysis, indicated that PT does not affect the basal GTPase activity of Gi, but blocks its activation by the photoreceptor. Taken together the results indicate that PT-mediated ADP ribosylation has two separate effects, one to block the interaction of receptor with Gi and another to impede the GTP-induced activation reaction from occurring, or that PT has only one effect, that of blocking interaction with receptors. In this latter case the present results add to a mounting series of data that are consistent with the hypothesis that unoccupied receptors are not inactive, but exhibit a basal agonist-independent activity responsible for the various effects of GTP observed on G protein-coupled effector functions in intact membranes.
Mol Endocrinol 1989 Jul
PMID:Studies on nucleotide and receptor regulation of Gi proteins: effects of pertussis toxin. 250 4

Previous studies had suggested the existence of nodulation (nod) genes downstream of nodG in Rhizobium meliloti strain 1021. We have established the DNA sequence and analyzed the translation products of the genes located in this position. Computer analysis of the DNA sequence revealed a number of overlapping putative open-reading frames (ORFs), so we constructed several clones that contained either full-length or truncated ORFs. The protein products of these clones were expressed in both R. meliloti and Escherichia coli in vitro transcription-translation systems. These assays unambiguously defined the expressed ORFs, which we named nodP and nodQ. In addition, we found homology to these genes, via Southern hybridizations, elsewhere in the genome of R. meliloti strain 1021, and in other species of Rhizobium. The nodP gene also displayed homology to E. coli. A computer search revealed significant homology between NodQ and the GDP binding domain of elongation factor Tu (EF-Tu).
Mol Plant Microbe Interact
PMID:Nucleotide sequence and protein products of two new nodulation genes of Rhizobium meliloti, nodP and nodQ. 252 Aug 20


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