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)

alpha 2-Macroglobulin (alpha 2M)-methylamine binding to macrophages appears to involve two receptors. Binding of alpha 2M-methylamine to low density lipoprotein-related protein (LRP) results in cellular uptake and degradation, while binding to a newly described alpha 2M signaling receptor elevates intracellular calcium ([Ca2+]i) and inositol phosphates. We now demonstrate that binding of lactoferrin, Pseudomonas exotoxin A, and lipoprotein lipase to LRP on macrophages results in increased [Ca2+]i and inositol 1,4,5-triphosphate. Receptor-associated protein, which binds to LRP but not the alpha 2M signaling receptor, blocks the lactoferrin signal but has no effect on alpha 2M-methylamine signaling. The latter observation supports our hypothesis that a distinct signaling receptor binds alpha 2M-methylamine. We further demonstrate that the signaling events induced by lactoferrin may involve a pertussis toxin-sensitive G protein, while the alpha 2M signaling receptor appears to be coupled to a pertussis toxin-insensitive G protein.
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PMID:The relationship between low density lipoprotein-related protein/alpha 2-macroglobulin (alpha 2M) receptors and the newly described alpha 2M signaling receptor. 751 27

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