Hormonal Inhibition of the Liver Plasma Membrane (Ca2+ —Mg2+ ) ATPase is Mediated by a Gs-like Protein
The calcium pump in liver plasma membrane, which is supported by a high-affinity calcium-activated ATPase (Lotersztajnet al., 1981, 1982; Pavoineet al., 1987), is responsible for extrusion of calcium out of the cell. We have shown that the liver Ca2+ pump is specifically inhibited by pharmacological concentrations of glucagon (Lotersztajnet al., 1984, 1985). This inhibition is independent of adenylate cyclase activation (Lotersztajnet al., 1984) and is probably unrelated to activation of phospholipase C by nanomolar concentrations of glucagon (Wakelamet al., 1986). The liver Ca2+ pump is also regulated by two proteins, an activator that directly stimulates activity of the purified (Ca2+ —Mg2+ ) ATPase (Lotersztajnet al., 1981), and a 30,000-Da inhibitor that interacts with the purified enzyme only in the presence of the activator and Mg2+ (Lotersztajn and Pecker, 1982) and that mediates enzyme inhibition by glucagon (Lotersztajnet al ., 1985). The question arose as to the possible analogy between these activator and inhibitor proteins of (Ca2+ —Mg2+ )ATPase and guanine nucleotide-binding (G) proteins.
KeywordsATPase Activity Adenylate Cyclase Cholera Toxin Malachite Green Pertussis Toxin
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