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Query: UNIPROT:P19086 (Galphaz)
 110 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High affinity binding sites for pancreastatin were identified for the first time, and their molecular characterization was performed with rat liver membranes. Using rat 125I-pancreastatin, we have studied the interaction of pancreastatin with liver membranes. Cross-linking of the tracer to the membranes was performed using the bifunctional reagent dithiobis(succinimidyl propionate). Analysis of binding under equilibrium conditions indicated the existence of one class of binding sites, with a Bmax of 15 fmol/mg of protein and an apparent Kd of 0.2 nM. The cross-linking of 125I-pancreastatin to liver membranes revealed a single band of M(r) 40,000, corresponding to the 125I-pancreastatin-receptor complex. The labeling of this complex was inhibited in the presence of rat pancreastatin (10(-10) to 10(-7) M) and in the presence of guanyl-5'-ylimidodiphosphate (10(-7) to 10(-4) M). Pretreatment of rat liver membranes with pertussis toxin did not affect pancreastatin binding or the inhibition by guanyl-5'-ylimidodiphosphate of pancreastatin binding. The specificity of pancreastatin binding was further assessed by displacement experiments with pancreastatin from other species and vasopressin. The binding of the pancreastatin-receptor complexes to Sepharose coupled to different lectins showed the glycoprotein nature of the pancreastatin receptor. These results strongly suggest that rat liver possesses a specific pancreastatin receptor, a glycoprotein of M(r) 35,000 that is coupled to a pertussis toxin-insensitive G protein in the plasma membrane.
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PMID:Receptors for pancreastatin in rat liver membranes: molecular identification and characterization by covalent cross-linking. 805 54

The whole-cell patch-clamp technique was used to investigate the effect of neurotensin on cholinergic neurons cultured from the rat nucleus basalis of Meynert. Neurotensin excited the neurons by inducing an initial inward current carried, at least in part, by Na+ and by reducing inwardly rectifying K+ conductance. Reduction of the inwardly rectifying K+ conductance was mediated by a pertussis toxin-insensitive G protein.
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PMID:Neurotensin excites basal forebrain cholinergic neurons: ionic and signal-transduction mechanisms. 814 99

v-Src-induced increases in diglyceride are derived from phosphatidylcholine via a type D phospholipase (PLD) and a phosphatidic acid phosphatase. v-Src-induced PLD activity, as measured by PLD-catalyzed transphosphatidylation of phosphatidylcholine to phosphatidylethanol, is inhibited by GDP beta S, which inhibits G-protein-mediated intracellular signals. Similarly, v-Src-induced increases in diglyceride are also blocked by GDP beta S. In contrast to the PLD activity induced by v-Src, PLD activity induced by the protein kinase C agonist, 12-O-tetradecanoylphorbol-13-acetate (TPA), was insensitive to GDP beta S. Consistent with the involvement of a G protein in the activation of PLD activity by v-Src, GTP gamma S, a nonhydrolyzable analog of GTP that potentiates G-protein-mediated signals, strongly enhanced PLD activity in v-Src-transformed cells relative to that in parental BALB/c 3T3 cells. The effect of GTP gamma S on PLD activity in v-Src-transformed cells was observed only when cells were prelabeled with [3H]myristate, which is incorporated exclusively into phosphatidylcholine, the substrate for the v-Src-induced PLD. There was no difference in the effect of GTP gamma S-induced PLD activity on v-Src-transformed and BALB/c 3T3 cells when the cells were prelabeled with [3H]arachidonate, which is not incorporated into phospholipids that are substrates for the v-Src-induced PLD. Similarly, GDP beta S inhibited PLD activity in v-Src-transformed cells much more strongly than in BALB/c 3T3 cells when [3H]myristate was used to prelabel the cells. The GTP-dependent activation of PLD by v-Src was dependent upon the presence of ATP but was unaffected by either cholera or pertussis toxin. These data suggest that v-Src induces PLD activity through a phosphorylation event and is mediated by a cholera and pertussis toxin-insensitive G protein.
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PMID:Evidence that v-Src-induced phospholipase D activity is mediated by a G protein. 819 11

alpha 1-Adrenergic receptors (ARs) are members of the G protein-coupled receptor superfamily. alpha 1-AR subtypes mediate the effects of the sympathetic nervous system, especially those involved in cardiac homeostasis. To investigate signal transduction by a novel subtype (alpha 1D), which we recently cloned, and to compare it with that by the previously characterized alpha 1B-AR, we assessed the ability of each subtype to activate polyphosphoinositide (PI) metabolism, cAMP accumulation, and arachidonic acid release in Chinese hamster ovary (CHO) and COS-1 cells expressing these subtypes after stable or transient transfection, respectively. In COS-1 and CHO cells, both the alpha 1D- and alpha 1B-AR were found to couple to PI hydrolysis through a pertussis toxin-insensitive G protein. Both alpha 1-AR subtypes also increased intracellular cAMP by an indirect mechanism, although this effect was observed only in COS-1 cells and not in CHO cells. Interestingly, alpha 1-AR-stimulated arachidonic acid release was also demonstrated for both subtypes in COS-1 cells. This release was mediated through phospholipase A2 activation and involved a pertussis toxin-sensitive G protein. alpha 1-AR-stimulated arachidonic acid release was dependent upon extracellular calcium and was inhibited by 1 microM nifedipine. Inhibitors of protein kinase C, phospholipase C, and diacylglycerol lipase did not alter alpha 1-AR-stimulated release of arachidonic acid. These findings indicate that in COS-1 cells alpha 1-AR-stimulated arachidonic acid release is most likely coupled to dihydropyridine-sensitive L-type calcium channels via a pertussis toxin-sensitive G protein. The influx of extracellular calcium then stimulates phospholipase A2 to release arachidonic acid. alpha 1-AR-stimulated arachidonic acid release could also be demonstrated in CHO cells and was pertussis toxin sensitive but nifedipine insensitive. These cells were also unresponsive to Bay K8644, indicating a lack of voltage-sensitive calcium channels in CHO cells. Nevertheless, alpha 1-AR activation increased intracellular Ca2+ levels, as assessed by fura-2 fluorescence studies. Neomycin blocked both alpha 1-AR-stimulated PI hydrolysis and increases in intracellular Ca2+ levels but did not inhibit the increase in arachidonic acid release. Taken together, these data indicate that in CHO cells alpha 1-ARs can couple directly to phospholipase A2 activation via a pertussis toxin-sensitive pathway. Thus, in these model systems we demonstrate for the first time that a single alpha 1-AR subtype can activate multiple distinct signal transduction pathways, in which receptor-effector coupling is modulated by distinct G proteins.
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PMID:Coupling of expressed alpha 1B- and alpha 1D-adrenergic receptor to multiple signaling pathways is both G protein and cell type specific. 823 29

In NG108-15 cells, bradykinin (BK) activates a potassium current (IK,BK) and inhibits the voltage-dependent calcium current (ICa,V). BK also stimulates a phosphatidylinositol-specific phospholipase C (PI-PLC). The subsequent release of inositol 1,4,5-trisphosphate and increase in intracellular calcium contribute to IK,BK, through activation of a calcium-dependent potassium current. In membranes from these cells, stimulation of PI-PLC by BK is mediated by Gq and/or G11, two homologous, pertussis toxin-insensitive G proteins. Here, we have investigated the role of Gq/11 in the electrical responses to BK. GTP gamma S mimicked and occluded both actions of BK, and both effects were insensitive to pertussis toxin. Perfusion of an anti-Gq/11 alpha antibody into the pipette suppressed IK,BK, but not the inhibition of ICa,V by BK. Thus, BK couples to IK,BK via Gq/11, but coupling to ICa,V is most likely via a different, pertussis toxin-insensitive G protein.
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PMID:Bradykinin modulates potassium and calcium currents in neuroblastoma hybrid cells via different pertussis toxin-insensitive pathways. 829 55

The insulin signalling pathway to control nuclear p33 gene expression was examined. An AlF4-stimulated pertussis toxin-insensitive G protein was shown to be involved. The action of AlF4- was completely blocked by deferoxamine. Insulin action was markedly stimulated in the presence of AlF4-. cAMP and diacylglycerol concentrations were examined as possible regulators but no increases were detected. The effects of AlF4- and of insulin were completely inhibited by the general kinase inhibitor H-7. A second calcium calmodulin protein kinase inhibitor, W-7, had no detectable effect. Insulin and AlF4- were shown to stabilize p33 mRNA.
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PMID:Mechanisms of aluminum fluoride- and insulin-stimulated p33 mRNA accumulation in rat hepatoma cells: involvement of a G protein and kinase action and demonstration of effects on mRNA turnover. 831 37

Cultured neurons from the CA1 and CA3 regions of the rat hippocampus were studied by using the whole-cell version of patch clamp. Application of acetylcholine (5-10 microM) or muscarine (20 microM) to a neuron with a holding potential of approximately -70 mV produced a slow inward current. This inward current was inhibited by atropine (1-2 microM). Loading the cell with GTP gamma S caused a change in the muscarinic response. In the control cells the muscarine-induced inward current recovered by 89%. On the other hand, in the GTP gamma S-loaded cells the inward current recovered by only 30%, indicating some irreversibility. Pertussis toxin treatment did not change the muscarine-induced slow inward current. Loading the cells with cyclic AMP (100 microM) plus IBMX (1 mM) (an inhibitor of phosphodiesterase) did not occlude the effect of muscarine. We conclude that the slow inward current is mediated through a pertussis toxin-insensitive G protein, and that cyclic AMP is not a part of the signal transduction cascade. The finding that the GTP gamma S-loaded cells did not show complete irreversibility was discussed in relation to the results of Benson et al. (J. Physiol., 404 (1988) 479-496), which showed that there are two ionic mechanisms responsible for the muscarine-induced depolarization. Occasionally cells were encountered, in which muscarine (or acetylcholine) evoked a large and rapid inward current, followed by the usual slow inward current. The time course of this rapid response was not affected by GTP gamma S.
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PMID:The role of G protein in muscarinic depolarization near resting potential in cultured hippocampal neurons. 839 28

We have shown that in bovine iris sphincter membranes G proteins are involved in coupling muscarinic-, PGF2 alpha-, endothelin- and platelet-activating factor receptors to the activation of phospholipase A2 and the release of arachidonic acid. GTP gamma S and GTP gamma S plus carbachol stimulated arachidonic acid release in the membranes in a dose- and time-dependent manner. Nucleotide stimulation was specific to GTP gamma S, since GDP, GDP beta S and ATP had no effect. The stimulatory effect of GTP gamma S plus carbachol was blocked by atropine and it required the presence of physiological concentrations of Ca2-. AIF4-, which bypasses the receptor and directly activates the G protein, induced arachidonic acid liberation in the intact iris sphincter, but was ineffective in the membranes. Addition of GTP gamma S plus carbachol to sphincter muscle membranes prelabeled with [3H]inositol or 3H-arachidonic acid resulted in the formation of lysophosphatidylinositol and the liberation of arachidonic acid, thus suggesting the involvement of phospholipase A2. In vitro treatment of the iris membranes with pertussis toxic inhibited arachidonic acid release by the agonists. This is in contrast to the pertussis toxin-insensitive G protein that activates phospholipase C in this tissue (22). These data demonstrate that in the iris sphincter a G protein is involved in the step between receptor activation and the activation of phospholipase A2, and that arachidonic acid release in this tissue is mediated by a pertussis-toxin-sensitive G protein-coupled phospholipase A2. Thus, GTP can regulate arachidonic acid release and its subsequent conversion into eicosanoids by stimulating its formation.
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PMID:Involvement of a pertussis toxin-sensitive G protein-coupled phospholipase A2 in agonist-stimulated arachidonic acid release in membranes isolated from bovine iris sphincter smooth muscle. 851 May 60

Involvement of a cGMP pathway in signal transduction stimulated by endothelins(ETs) and sarafotoxins (SRTXs) was examined in rat atrial slices. These peptides activated different receptor-binding sites (ET-1 and SRTX-b reacted with picomolar binding sites of the ET(A) receptor, and ET-3 and SRTX-c reacted with the nanomolar binding sites of the ET(B) receptor) to produce cGMP. ET-1 and SRTX-b stimulated an increase in cGMP levels via a Ca2+-dependent NO pathway involving a pertussis toxin-insensitive G protein, whereas ET-3 and SRTX-c elevated cGMP levels via a Ca2+-independent CO pathway involving a pertussis toxin-sensitive G protein. These results can best be explained in terms of formation of different ligand-receptor-G-protein complexes. The ligands had no effect on ventricular slices, indicating that these signal transduction mechanisms are unique to the atria.
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PMID:cGMP formation in rat atrial slices is ligand and endothelin receptor subtype specific. 859 1

p21 ras plays as important role in cell proliferation, transformation and differentiation. Recently, the requirement of p21 ras has been suggested for cellular responses induced by stimulation of heterotrimeric G protein-coupled receptors. However, it remains to be determined how agonists for G protein-coupled receptors activate p21 ras in metazoans. We show here that stimulation of the G q protein-coupled angiotensin II (Ang II) receptor causes activation of p21 ras in cardiac myocytes. The p21 ras activation by Ang II is mediated by an increase in the guanine nucleotide exchange activity, but not by an inhibition of the GTPase-activating protein. Ang II causes rapid tyrosine phosphorylation of Shc and its association with Grb2 and mSos-1, a guanine nucleotide exchange factor of p21 ras. This leads to translocation of mSos-1 to the membrane fraction. Shc associates with the SH3 domain of Fyn whose tyrosine kinase activity is activated by Ang II with a similar time course as that of tyrosine phosphorylation of Shc. Ang II-induced increase in the guanine nucleotide exchange activity was inhibited by a peptide ligand specific to the SH3 domain of the Src family tyrosine kinases. These results suggest that an agonist for a pertussis toxin-insensitive G protein-coupled receptor may initiate the cross-talk with non-receptor-type tyrosine kinases, thereby activating p21 ras using a similar mechanism as receptor tyrosine kinase-induced p21 ras activation.
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PMID:The heterotrimeric G q protein-coupled angiotensin II receptor activates p21 ras via the tyrosine kinase-Shc-Grb2-Sos pathway in cardiac myocytes. 863 Dec 99


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