The fungal teratogen secalonic acid D is an inhibitor of protein kinase C and of cyclic AMP-dependent protein kinase.
The teratogenic metabolite secalonic acid D deriving from the ergot-producing, rye-infecting ascomycete fungus Claviceps purpurea and from Penicillum oxalicum is an inhibitor of Ca2+- and phospholipid-dependent protein kinase C (PKC) and of the catalytic subunit of cyclic AMP-dependent protein kinase (cAK) (C50 values 15 microM and 12 microM, respectively). Secalonic acid D also inhibits Ca2+-calmodulin-dependent myosin light chain kinase (MLCK) and plant Ca2+-dependent protein kinase (CDPK). The inhibition of cAK by secalonic acid D is competitive with respect to both peptide substrate and ATP. However, secalonic acid D does not inhibit a high-affinity nucleotide-binding phosphatase from potato. A variety of other naturally-occurring teratogenic agents are not inhibitors of the protein kinases examined.
Wang
B H
BH
School of Biochemistry, La Trobe University, Victoria, Australia.
Polya
G M
GM
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000201:enzymology; D002645:Chickens; D002967:Claviceps; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D005895:Gizzard, Avian; D007700:Kinetics; D008969:Molecular Sequence Data; D009183:Mycotoxins / Q000302:isolation & purification / Q000494:pharmacology*; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors; D009842:Oligopeptides / Q000494:pharmacology; D010407:Penicillium; D010446:Peptide Fragments / Q000138:chemical synthesis; D010944:Plants; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D047428:Protein Kinase Inhibitors; D051381:Rats; D013723:Teratogens / Q000302:isolation & purification / Q000494:pharmacology*; D014966:Xanthenes / Q000302:isolation & purification / Q000494:pharmacology*; D044004:Xanthones
D004791:Enzyme Inhibitors; D009183:Mycotoxins; D009842:Oligopeptides; D010446:Peptide Fragments; D047428:Protein Kinase Inhibitors; D013723:Teratogens; D014966:Xanthenes; D044004:Xanthones; C009218:secalonic acid; C037642:kemptide; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D009219:Myosin-Light-Chain Kinase