Inhibition of mammalian protein kinase and phosphodiesterase activities by a cyclic AMP-like compound isolated from higher plants.
A cyclic AMP-like substance has been isolated from higher plant tissues which can be quantitated with the use of a radioimmunoassay similar to that described by A. L. Steiner, D. M. Kipnis, R. Utiger, and C. Parker [(1969) Proc. Natl. Acad. Sci. USA 64, 367-373]. This compound has been extensively purified and is chromatographically distinct from authentic cyclic AMP. This cyclic AMP-like compound inhibited beef heart 3':5'-cyclic-nucleotide phosphodietsterase (3':5'-cyclic-nucleotide 5'-nucleotidohydrolase, EC 3.1.4.17), with half-maximal inhibition occurring at a concentration of 7.6 X 10(-10) M cyclic AMP equivalents. The compound also inhibited cyclic AMP-dependent protein kinase (ATP:protein phosphotransferase; EC 2.7.1.37) from bovine heart, with half-maximal inhibition of mixed histone phosphorylation occurring at 8.0 X 10(-11) M cyclic AMP equivalents. Equipotent inhibition of phosphorylation and associated trace ATPase activity were observed with the purified catalytic subunit of cyclic AMP-dependent protein kinase from calf thymus with a synthetic heptapeptide as substrate. Moreover, steady-state kinetic analysis of this inhibition in the latter system showed it to be nonlinear and noncompetitive versus MgATP.
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002417:Cattle; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D046911:Macromolecular Substances; D009206:Myocardium / Q000201:enzymology; D010726:Phosphodiesterase Inhibitors / Q000302:isolation & purification*; D010944:Plants / Q000201:enzymology*; D047428:Protein Kinase Inhibitors
D046911:Macromolecular Substances; D010726:Phosphodiesterase Inhibitors; D047428:Protein Kinase Inhibitors; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D000251:Adenosine Triphosphatases