Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P19086 (Galphaz)
 110 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sperm-mediated egg activation may be analogous to ligand-mediated signal transduction through G protein-coupled receptors. We investigated this possibility in the mouse egg by microinjecting mouse oocytes with an m1 muscarinic receptor mRNA. Following oocyte maturation in vitro, the metaphase II-arrested eggs were treated with acetylcholine and its effect was examined on zona pellucida modifications and pronuclear formation, which are end points of early and late egg activation, respectively. Treatment of these eggs with acetylcholine reveals that both the ZP2 to ZP2f conversion and pronuclear formation occur. Atropine and microinjected GDP beta S block the acetylcholine-induced ZP2 conversion, suggesting that the acetylcholine effects are mediated via a functional G protein-coupled m1 receptor. The acetylcholine-induced ZP2 conversion, however, is not inhibited by pertussis toxin under conditions in which greater than 90% of the endogenous Gi is inactivated by ADP ribosylation. The presence of a pertussis toxin-insensitive G protein, Gq, is detected by immunoblotting; this G protein could be a candidate to mediate the pertussis toxin-insensitive effects of acetylcholine. Results of these experiments are consistent with the hypothesis that receptor-mediated G protein activation may play a role in egg activation.
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PMID:Role of G proteins in mouse egg activation: stimulatory effects of acetylcholine on the ZP2 to ZP2f conversion and pronuclear formation in eggs expressing a functional m1 muscarinic receptor. 157 93

The effects of adenosine receptor agonists and antagonists on field-stimulated release of radioactivity from superfused guinea-pig papillary muscles preincubated with [3H] noradrenaline were studied. N6-cyclopentyladenosine (CPA), N6-(R-phenylisopropyl)-adenosine, and 5'-N-ethylcarboxamidoadenosine caused concentration-dependent inhibition of evoked overflow with a rank order of potency typical for interaction of the compounds with the A1-subtype of adenosine receptors. Maximum inhibition was 80%. The A1-selective antagonist 8-cyclopentyl-1,3-dipropyl-xanthine (DPCPX) induced a rightward shift of the concentration-response curve for CPA with a pA2 of 8.35. However, DPCPX per se had no effect on stimulation-evoked tritium overflow. On the other hand, in the presence of 4-nitrobenzylthioinosine (2 mumol/l) and deoxycoformycin (1 mumol/l), inhibitors of adenosine uptake and deamination, respectively, DPCPX produced a concentration-dependent increase in overflow with a pD2 of 8.1. Pretreatment of the animals with pertussis toxin caused a substantial reduction in the activity of toxin-sensitive G proteins, as indicated by a lack of [32P]ADP ribosylation in a ventricular membrane preparation. Nevertheless, the inhibitory effect of the adenosine receptor agonists on stimulus-evoked overflow remained unaffected. These results are compatible with the existence of inhibitory prejunctional adenosine receptors in guinea-pig papillary muscle, which appear to be coupled to a pertussis toxin-insensitive G protein. The role of endogenous adenosine in occupying these receptors seems minimal under basal conditions.
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PMID:Adenosine receptors mediate a pertussis toxin-insensitive prejunctional inhibition of noradrenaline release on a papillary muscle model. 190 20

Ca2+-mobilizing agonists stimulate phospholipase C-mediated phosphatidylinositol 4,5-bisphosphate hydrolysis and inositol trisphosphate (IP3) formation in pulmonary as well as in peripheral vascular endothelial cells (EC). In general, it is believed that receptor-phospholipase C interactions involve a guanine nucleotide regulatory (G) protein. This interaction can be inhibited by Bordetella pertussis toxin in certain cells. Here we report that pertussis toxin catalyzes the [32P]ADP ribosylation of a Mr = 41,000 protein in human umbilical vein EC. However, prior EC treatment with pertussis toxin (250 ng/ml for 20 h) does not inhibit thrombin-induced Ca2+ flux or IP3 formation, despite markedly attenuating the radiolabeling of the Mr = 41,000 protein (less than 5% control). Treatment of digitonin-permeabilized human umbilical vein EC with GTP gamma S, a stable GTP analog, or AIF4-, but not with GDP beta S, stimulates IP3 accumulation. However, GDP beta S inhibits GTP gamma S-induced IP3 accumulation. Although thrombin alone is not very effective in elevating IP3 levels in permeabilized EC, thrombin and GTP gamma S act in a synergistic fashion to increase IP3 accumulation. Overall, these observations are interpreted to indicate that a pertussis toxin-insensitive G protein is a key intermediate in the signaling pathway linking thrombin receptors to phospholipase C in human umbilical vein EC.
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PMID:GTP gamma S increases thrombin-mediated inositol trisphosphate accumulation in permeabilized human endothelial cells. 255 82

Heterotrimeric (alphabetagamma) G proteins interact with sensory receptors to transduce signals to downstream effectors in eukaryotes. We previously reported that GNA-1 from Neurospora crassa is a microbial member of the Galphai family found in higher organisms. Deletion of gna-1 leads to female sterility, slower growth rates on normal and hyperosmotic solid medium, and increased resistance to heat and oxidative stress. In this study we compare mammalian genes for proteins of the Galphai sub-family (Galphai, Galphao, Galphat and Galphaz), and Galphas (which is not a member of the Galphai family) with the N. crassa gna-1 gene with respect to their ability to complement deltagna-1 phenotypes. Northern analysis detected full-length transcripts of all these genes, except that for Galphai, in N. crassa transformants. Measurements of pertussis toxin-catalyzed ADP-ribosylation and Western analysis showed that the GNA-1, Galphaz, Galphao and Galphas proteins were present in the respective transformed strains. Strains in which the mammalian Galpha protein could be detected were subjected to phenotypic testing. During the vegetative cycle, none of the mammalian Galpha genes complemented the thermotolerance phenotype of deltagna-1. However, the three expressed mammalian Galpha genes achieved at least partial complementation of the defects in vegetative apical extension rate. cAMP levels did not correlate with restoration of vegetative growth rate by the mammalian genes. During the sexual cycle, Galphao was the only mammalian Galpha gene that rescued the defect in female fertility characteristic of deltagna-1 strains. Alignment of GNA-1, Galphaz, Galphao and Galphas protein sequences revealed correlations between the observed complementation pattern and the degree of identity to GNA-1 in various functional motifs. The finding that Galphac gave the best restoration of vegetative growth but could not restore normal female fertility implies that GNA-1 regulates different pathways that are important for vegetative and sexual growth in N. crassa.
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PMID:Differential complementation of a Neurospora crassa Galpha(i) mutation using mammalian Galpha protein genes. 1085 94

Replacement of beta6/alpha5 region at the C-terminus on Galpha16 with Galphaz-specific residues has been shown to broaden the promiscuity of Galpha16. Here, we substituted the last 44 residues of Galpha16 with the corresponding region from either Galphai2 or GalphaoA (16i44 and 16o44). 16i44 and 16o44 chimeras were more effective than Galpha16 at coupling to Gi-linked delta-opioid, mu-opioid, and Xenopus melatonin MT1c receptors when coexpressed in green monkey fibroblast (COS-7) cells. 16i44, but not 16o44, also enhanced the formyl peptide-induced stimulation of phospholipase C activity. Both chimeras were resistant to pertussis toxin-catalyzed [32P]ADP-ribosylation, despite the fact that pertussis toxin partially inhibited the chimera-mediated stimulation of phospholipase Cbeta. The use of Galphat1 as a Gbetagamma scavenger revealed that the pertussis toxin-sensitivity can be attributed to endogenous Gbetagamma subunits released from G(i/o). Although incorporation of a Galphai-like beta6/alpha5 region into the C-terminus of Galpha16 increases its promiscuity, this region is not sufficient to support recognition by pertussis toxin.
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PMID:The beta6/alpha5 regions of Galphai2 and GalphaoA increase the promiscuity of Galpha16 but are insufficient for pertussis toxin-catalyzed ADP-ribosylation. 1289 27