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

We have previously demonstrated that human bronchial smooth muscle cells possess a single class of high-affinity binding sites for endothelin 1. In this study, we further characterized the receptor for endothelin 1 and evaluated the signal transduction mechanisms of this peptide. Stimulation of cultured human bronchial smooth muscle cells with endothelin 1 induced mobilization of Ca2+ from both intracellular and extracellular pools with a biphasic increase in cytoplasmic free Ca2+ concentration. Endothelin 1 increased cellular levels of inositol phosphates and diacylglycerol, indicating activation of phospholipase C, but induced production of inositol phosphates in smooth muscle cell membranes only in the presence of guanosine 5'-O-(thiotriphosphate) (GTP gamma S). Treatment of smooth muscle cells with pertussis toxin failed to block the endothelin 1-induced increase in inositol phosphate production and Ca2+ mobilization. These results suggest that the receptor for endothelin 1 in bronchial smooth muscle is coupled to phospholipase C through a pertussis toxin-insensitive G protein. Affinity crosslinking experiments identified the endothelin 1 receptor as a single band with an apparent molecular weight of approximately 70,000 on sodium dodecyl sulfate polyacrylamide gel electrophoresis, further supporting the functional evidence that endothelin 1 receptor belongs to the G protein-linked rhodopsin type of receptor superfamily.
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PMID:Mechanisms of calcium mobilization and phosphoinositide hydrolysis in human bronchial smooth muscle cells by endothelin 1. 165 61

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

By site-directed mutagenesis, three cysteine residues (amino acids 402, 403, and 405) in the carboxyl terminus of human endothelinB (ETB) were identified as potential palmitoylation sites. Substitutions of all of the three cysteine residues with serine gave an unpalmitoylated mutant, C2S/C3S/C5S. When expressed in Chinese hamster ovary cells, C2S/C3S/C5S was localized on the cell surface, retained high affinities to ET-1 and ET-3, and was rapidly internalized when bound to the ligand. However, unlike the wild-type ETB, C2S/C3S/C5S transmitted neither an inhibitory effect on adenylate cyclase nor a stimulatory effect on phospholipase C, indicating a critical role of palmitoylation in the coupling with G proteins, regardless of the G protein subtypes. Truncation of the carboxyl terminus including Cys403/Cys405 gave a deletion mutant Delta403 that was palmitoylated on Cys402 and lacked the carboxyl terminus downstream to the palmitoylation site. Delta403 did transmit a stimulatory effect on phospholipase C via a pertussis toxin-insensitive G protein but it failed to transmit an inhibitory effect on adenylate cyclase. These results indicated a differential requirement for the carboxyl terminus downstream to the palmitoylation site in the coupling with G protein subtypes, i.e. it is required for the coupling with Gi but not for that with Gq.
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PMID:Palmitoylation of human endothelinB. Its critical role in G protein coupling and a differential requirement for the cytoplasmic tail by G protein subtypes. 926 Nov 80

In this present study, the effects of ET-1 on intracellular free calcium concentration ([Ca2+]i) and the underlying mechanisms were investigated in cultured neonatal rat myocardial cells loaded with fura-2/AM. The results are as follows. ET-1 induced an increase of [Ca2+]i in a dose-dependent manner, which consisted of a transient and sustained phase. BQ123, a selective ETA receptor antagonist, blocked the ET-1 induced [Ca2+]i responses, suggesting that these responses were mediated by ETA receptors. After removal of extracellular Ca2+, ET-1 induced the transient increase of [Ca2+]i without the sustained change. Protein kinase C (PKC) agonist PMA attenuated the ET-1 induced transient [Ca2+]i increase. Amiloride and nifedipine did not block the [Ca2+]i change induced by ET-1. After pretreatment of myocardial cells with pertussis toxin, ET-1 also induced the transient increase of [Ca2+]i but did not affect the sustained increase. These results suggest that the transient [Ca2+]i increase may involve pertussis toxin-insensitive G protein and the sustained one may be caused by extracellular calcium influx, in which pertussis toxin sensitive G protein is involved. Furthermore, PKC, but not Na+/H+ exchange, plays an important role in these effects.
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PMID:[Effect of ET-1 on intracellular free calcium in cultured neonatal myocardial cells]. 1149 66