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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenylate cyclase activity and binding of neurotransmitters to some receptors can be modulated simultaneously by guanine nucleotides. Furthermore it has been shown, in different neurotransmitter systems, that the ability of GTP to inhibit agonist binding is related to the capacity of the transmitter to modulate adenylate cyclase activity. In the present report we show that in chick optic tectum and cerebellum the effects of guanine nucleotides on kainic acid binding and on adenylate cyclase activity can be dissociated. In lysed membrane preparations, GTP, GDP, and GMP, or their analogs, displace binding of kainic acid with the same efficiency, whereas only GTP stimulates adenylate cyclase. In vesicle preparations, all three nucleotides inhibit binding of kainic acid without modifying adenylate cyclase activity. The present results suggest that, if adenylate cyclase is indeed coupled to this particular type of excitatory amino acid receptor, the coupling mechanism would be probably different from those operating in other neurotransmitter systems and also that the displacement of kainic acid by GDP and GMP (and even perhaps by GTP) is not likely to depend on the interaction between the receptor and a Gs-protein-mediated effector system.
J Mol Neurosci 1991
PMID:Effects of guanine nucleotides on kainic acid binding and on adenylate cyclase in chick optic tectum and cerebellum. 165 2

The role of guanine nucleotide-binding proteins in the induction of prostacyclin synthesis by stimulated endothelial cells is incompletely understood. We report that sodium fluoride (NaF), a potent activator of cellular guanine nucleotide-binding proteins, affected time- and concentration-dependent generation of prostacyclin (PGI2) by cultured human umbilical vein endothelial cells without evidence of cellular toxicity detected by 51Cr or lactate dehydrogenase release. PGI2 synthesis by NaF-stimulated endothelial cells was associated with increases in arachidonate release, phosphoinositide hydrolysis, generation of inositol phosphates, and accumulation of diacylglycerol. These responses to NaF, as well as alpha-thrombin-mediated responses, were not dependent upon the availability of extracellular free Ca2+ but were associated with the mobilization of stored intracellular Ca2+ detected by the luminescence of the photoprotein aequorin. Neither PGI2 synthesis nor Ca2+ responses following alpha-thrombin or NaF stimulation were inhibited by pretreatment of cells with the islet activating protein from Bordetella pertussis but were significantly attenuated by the G protein inhibitor GDP beta S in permeabilized cells. Our results are compatible with a model wherein NaF directly activates a phosphoinositidase-linked guanine nucleotide regulatory protein, Gp, in human umbilical vein endothelial cell monolayers. This activation results in phosphoinositide hydrolysis, Ca2+ mobilization, arachidonate release, and subsequent functional activation, assessed by PGI2 release. Biologically relevant agonists such as alpha-thrombin may exert their influence on arachidonate metabolism, in part, by promoting receptor-dependent activation of this G protein.
Am J Respir Cell Mol Biol 1991 Aug
PMID:Sodium fluoride induces phosphoinositide hydrolysis, Ca2+ mobilization, and prostacyclin synthesis in cultured human endothelium: further evidence for regulation by a pertussis toxin-insensitive guanine nucleotide-binding protein. 165 60

The molecular mechanism of reduced incorporation of radioactively labeled mannose into hamster liver glycoconjugates during the progression of vitamin A deficiency was investigated. In particular the in vivo incorporation of [2-3H]mannose into GDP-mannose, dolichyl phosphate mannose (Dol-P-Man), lipid-linked oligosaccharides, and glycopeptides of hamster liver was examined. Hamsters maintained on a vitamin A-free diet showed a reduction in the incorporation of mannose into GDP-mannose about 10 days before clinical signs of vitamin A deficiency could be observed. The decrease in [2-3H]mannose incorporated into GDP-mannose was accompanied by a reduction in label incorporated into Dol-P-Man, lipid linked oligosaccharides and glycopeptides, which became more severe with the progression of vitamin A deficiency. By the time they reached a plateau stage of growth, hamsters fed the vitamin A-free diet showed a 50% reduction in the amount of [2-3H]mannose converted to GDP-mannose, and the radioactivity associated with Dol-P-Man and glycopeptides was reduced by approximately 60% as compared to retinoic acid-supplemented controls. These results strongly indicate that the reduced incorporation of mannose into lipidic intermediates and glycoproteins observed during vitamin A deficiency is due to impaired GDP-mannose synthesis.
Mol Cell Biochem 1990 Mar 27
PMID:Reduced mannose incorporation into GDP-mannose and dolichol-linked intermediates of N-glycosylation in hamster liver during vitamin A deficiency. 169 71

GTPase-activating protein (GAP) is a cytosolic protein that stimulates the rate of hydrolysis of GTP (GTP to GDP) bound to normal p21ras, but does not catalyze the hydrolysis of GTP bound to oncogenic, activated forms of the ras protein. Transformation of cells with v-src or activated transforming variants of c-src or stimulation of cells with epidermal growth factor resulted in the stable association of GAP with two tyrosine-phosphorylated cellular proteins of 64 kDa (p64) and 190 kDa (p190). Analysis of GAP immune complexes isolated from extracts of metabolically labeled src-transformed cells and epidermal growth factor-stimulated cells indicated that tyrosine phosphorylation of p64 and p190 appeared to be coincident with the stable association of these proteins with GAP. Quantitation of the amount of p64 associated with GAP in v-src-transformed cells, however, indicated that only 15 to 25% of tyrosine-phosphorylated p64 was found in complex with GAP. Mutations within the SH2 region of pp60src that render activated pp60src defective for transformation inhibited the efficient formation of complexes between GAP and the tyrosine-phosphorylated forms of p64 and p190. From these data, we suggest that tyrosine phosphorylation and stable association of p64 with GAP is an important step in mediating cellular signaling through the p21ras-GAP pathway.
Mol Cell Biol 1991 Feb
PMID:Transformation by pp60src or stimulation of cells with epidermal growth factor induces the stable association of tyrosine-phosphorylated cellular proteins with GTPase-activating protein. 170 33

We report the presence in Salmonella enterica strain LT2 (serovar thyphimurium) of duplicate genes for two steps in the synthesis of GDP-mannose. The previously known genes, rfbK (phosphomannomutase) and rfbM (mannose-1-phosphate guanyltransferase), are part of the gene cluster for the O antigen. The two new genes, cpsB and cpsG, respectively, are thought to be part of the gene cluster for the M antigen capsular polysaccharide, present in many Enterobacteriaceae. The two genes have been sequenced and have a GC content of 0.61, suggesting an origin outside of Salmonella. Comparison of the inferred protein sequences for cpsB and rfbM shows 57% identity of amino acids whereas for cpsG and rfbK there is only 19% identity. It is suggested that the greater divergence between cpsG and rfbK may be due to a period of accelerated evolution, perhaps precipitated by transfer of the genes from another species.
Mol Gen Genet 1991 Jun
PMID:The cps gene cluster of Salmonella strain LT2 includes a second mannose pathway: sequence of two genes and relationship to genes in the rfb gene cluster. 171 67

The primary structures of interferon (IFN)-induced guanylate-binding proteins (GBPs) were deduced from cloned human and murine cDNAs. These proteins contained only two of the three sequence motifs typically found in GTP/GDP-binding proteins. The N(T)KXD motif, which is believed to confer guanine specificity in other nucleotide-binding proteins, was absent. Nevertheless, the IFN-induced GBPs exhibited a high degree of selectivity for binding to agarose-immobilized guanine nucleotides. An interesting feature of IFN-induced GBPs is that they strongly bound to GMP agarose in addition to GDP and GTP agaroses but failed to bind to ATP agarose and all other nucleotide agaroses tested. Both GTP and GMP, but not ATP, competed for binding of murine GBP-1 to agarose-immobilized GMP. The IFN-induced GBPs thus define a distinct novel family of proteins with GTP-binding activity. We further demonstrate that human and murine cells contain at least two genes encoding IFN-induced GBPs. The cloned murine cDNA codes for GBP-1, an IFN-induced protein previously shown to be absent from mice of Gbp-1b genotype.
Mol Cell Biol 1991 Sep
PMID:Interferon-induced guanylate-binding proteins lack an N(T)KXD consensus motif and bind GMP in addition to GDP and GTP. 171 24

We show by nuclear magnetic resonance studies that, following GTP hydrolysis during phage T4 sheath contraction, GDP remains bound to the sheath protein (gp18), whereas orthophosphate is released. gp18 in the contracted state has GTPase activity and can hydrolyse exogenous GTP; the reaction is calcium-dependent and displays high substrate specificity. The process comprises two steps: (1) displacement of GDP from gp18 by exogenous GTP, and (2) GTP hydrolysis proper. The first step appears to be rate-limiting and to be accelerated when the nucleotide-protein interaction is mechanically disrupted by sonication.
J Mol Biol 1992 Jan 05
PMID:GTPase activity of bacteriophage T4 sheath protein. 173 Oct 71

The activity, stability and structure in solution of polypeptide elongation factor hEF-Tu from Halobacterium marismortui have been investigated. The protein is stable in aqueous solutions only at high concentrations of NaCl, KCl or ammonium sulphate, whereas it is more active in exchanging GDP at lower salt concentrations. It is more active and stable at lower pH values than is non-halophilic EF-Tu. The structure in solution of the protein was determined by complementary density, ultracentrifugation, dynamic light-scattering and neutron-scattering measurements. The protein has large hydration interactions, similar to those of other halophilic proteins: 0.4 (+/- 0.1) g of water and 0.20 (+/- 0.05) g of KCl associated with 1 g of protein, with a water/KCl mass ratio always remaining close to 2. The kinetics of inactivation at low salt concentrations showed a stabilizing effect of NaCl when compared to KCl. At low salt concentration, inactivation, protein unfolding and aggregation were strongly correlated. The results suggest that the stabilization model proposed for halophilic malate dehydrogenase by Zaccai et al., involving extensive protein interactions with hydrated salt ions, is also valid for hEF-Tu.
J Mol Biol 1992 Jan 05
PMID:Solution studies of elongation factor Tu from the extreme halophile Halobacterium marismortui. 173 Oct 81

Regulation of GTP and GDP binding and GTPase activity of cardiac sarcolemmal guanine nucleotide-binding proteins was investigated. In purified sarcolemmal membranes, carbachol and a variety of other muscarinic receptor (MR) agonists induced increases in [3H]GTP, [gamma-32P]GTP, and [3H]GDP binding to relatively high affinity sites. Carbachol-dependent GTP and GDP binding changes were maximal within 5 sec at 30 degrees and thereafter remained at steady state. Carbachol increased GTP binding to two sites with apparent Kapp values of 50 nM and 250 nM and GDP binding to a single site with a Kapp of 100 nM. N-Ethylmaleimide attenuated carbachol-dependent GDP and GTP binding, tentatively identifying the binding sites as Gi and/or Go. Further studies showed that [3H]GDP and [3H]GTP bound to Gi/Go in the presence of carbachol rapidly exchanged with GTP and GDP in the medium. In membranes preincubated with carbachol and [gamma-32P]GTP or carbachol and [3H]GDP, postaddition of atropine resulted in complete hydrolysis of [gamma-32P]GTP bound to Gi/Go, to unlabeled GDP and 32Pi, by GTPase, within 10 sec, whereas [3H]GDP remained bound. This study also showed that bound [3H]GDP did not exchange with GDP or GTP in the absence of an MR agonist. Under identical conditions, atropine reversed adenylate cyclase (AC) inhibition by carbachol and GTP or GDP in 5-10 sec. MR agonists appear to increase the rate of dissociation of GDP from Gi/Go, which results in rapid GTP turnover on these sites by a combination of GTPase and GDP/GTP exchange reactions. Furthermore, MR-Gi/Go may be tightly coupled during AC inhibition, so that GTP hydrolysis as well as MR-Gi/Go uncoupling may be required to reverse AC inhibition.
Mol Pharmacol 1992 Jan
PMID:Regulation of GDP and GTP binding in cardiac sarcolemma by muscarinic receptor agonists. 173 18

The Saccharomyces cerevisiae ras-like gene RSR1 is particularly closely related to the mammalian gene Krev-1 (also known as smg21A and rap1A). RSR1 was originally isolated as a multicopy suppressor of a cdc24 mutation, which causes an inability to bud or establish cell polarity. Deletion of RSR1 itself does not affect growth but causes a randomization of bud position. We have now constructed mutant alleles of RSR1 encoding proteins with substitutions of Val for Gly at position 12 (analogous to constitutively activated Ras proteins) or Asn for Lys at position 16 (analogous to a dominant-negative Ras protein). rsr1Val-12 could not restore a normal budding pattern to an rsr1 deletion strain but could suppress a cdc24 mutation when overexpressed. rsr1Asn-16 could randomize the budding pattern of a wild-type strain even in low copy number but was not lethal even in high copy number. These and other results suggest that Rsr1p functions only in bud site selection and not in subsequent events of polarity establishment and bud formation, that this function involves a cycling between GTP-bound and GDP-bound forms of the protein, and that the suppression of cdc24 involves direct interaction between Rsr1p[GTP] and Cdc24p. Functional homology between Rsr1p and Krev-1 p21 was suggested by the observations that expression of the latter protein in yeast cells could both suppress a cdc24 mutation and randomize the budding pattern of wild-type cells. As Krev-1 overexpression can suppress ras-induced transformation of mammalian cells, we looked for effects of RSR1 on the S. cerevisiae Ras pathway. Although no suppression of the activated RAS2Val-19 allele was observed, overexpression of rsr1Val-12 suppressed the lethality of strains lacking RAS gene function, apparently through a direct activation of adenyl cyclase. This interaction of Rsr1p with the effector of Ras in S. cerevisiae suggests that Krev-1 may revert ras-induced transformation of mammalian cells by affecting the interaction of ras p21 with its effector.
Mol Cell Biol 1992 Feb
PMID:RSR1, a ras-like gene homologous to Krev-1 (smg21A/rap1A): role in the development of cell polarity and interactions with the Ras pathway in Saccharomyces cerevisiae. 173 42


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