Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to see whether the receptor for cardiac glycosides might be localized upon or within the plasma membrane of digitalis-sensitive cells. Ouabain and digoxin were joined covalently to several large protein molecules. These macromolecular conjugates are too large to enter intact cells; consequently, any pharmacologic or biochemical effects which they display should arise from interaction with a cell surface receptor. Conjugates were tested in several cardiac glycoside-sensitive systems: (a), contractility response of isolated cardiac muscle; (b), active (86)Rb(+) uptake by red cells; (c), enzymatic activity of isolated myocardial microsomal (Na(+) + K(+))-activated adenosine triphosphatase (ATPase); and (d), enzymatic activity of solubilized red cell (Na(+) + K(+))-activated ATPase. Results demonstrated that in all of these systems, the macromolecular-glycoside conjugates were 100- to 1000-fold less active than the free glycosides. Careful chromatographic examination of the various conjugates revealed that they contained a small but persistent free cardiac glycoside contaminant. The amount of this species ranged from 0.1 to 1.0% of the total macromolecule-bound glycoside, and its presence fully explains the levels of biologic activity observed with the conjugates. To try to minimize steric factors which could interfere with glycoside-receptor interaction, digoxin and ouabain were also coupled to macromolecule via long, flexible polyamide side-chains. These extended chain conjugates, in which the cardiac glycoside potentially lay some 30 A removed from the surface of the macromolecule, also exhibited negligible digitalis-like effects when tested upon isolated cardiac muscle, red cell (86)Rb(+) uptake, and enzymatic activity of cardiac microsomal (Na(+) + K(+))-ATPase. However, the extended chain conjugates were fully active when examined with the solubilized red cell (Na(+) + K(+))-ATPase system. To further ensure that the chemical reactions used to couple macromolecule to glycoside did not inactivate the drug, all conjugates were subjected to extensive proteolytic digests exhibited full pharmacologic activity. Digoxin was also coupled to the tripeptide alanylglycylglycine, and the resulting conjugate was fully active. Taken together, these results suggest that if the receptor(s) for cardiac glycosides is associated with the plasma membrane, then it may lie deep within it.
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PMID:Studies on the localization of the cardiac glycoside receptor. 426 Jun 87

Plant cells are immobile; thus, plant growth and development depend on cell expansion rather than cell migration. The molecular mechanism by which the plasma membrane initiates changes in the cell expansion rate remains elusive. We found that a secreted peptide, RALF (rapid alkalinization factor), suppresses cell elongation of the primary root by activating the cell surface receptor FERONIA in Arabidopsis thaliana. A direct peptide-receptor interaction is supported by specific binding of RALF to FERONIA and reduced binding and insensitivity to RALF-induced growth inhibition in feronia mutants. Phosphoproteome measurements demonstrate that the RALF-FERONIA interaction causes phosphorylation of plasma membrane H(+)-adenosine triphosphatase 2 at Ser(899), mediating the inhibition of proton transport. The results reveal a molecular mechanism for RALF-induced extracellular alkalinization and a signaling pathway that regulates cell expansion.
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PMID:A peptide hormone and its receptor protein kinase regulate plant cell expansion. 2445 38