Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Brain / enzymology
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Chickens
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Claviceps
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Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors*
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Enzyme Inhibitors / isolation & purification
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Enzyme Inhibitors / pharmacology*
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Gizzard, Avian
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Kinetics
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Molecular Sequence Data
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Mycotoxins / isolation & purification
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Mycotoxins / pharmacology*
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Myosin-Light-Chain Kinase / antagonists & inhibitors
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Oligopeptides / pharmacology
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Penicillium
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Peptide Fragments / chemical synthesis
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Plants
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Protein Kinase C / antagonists & inhibitors*
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Protein Kinase Inhibitors*
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Rats
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Teratogens / isolation & purification
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Teratogens / pharmacology*
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Xanthenes / isolation & purification
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Xanthenes / pharmacology*
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Xanthones*
Substances
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Enzyme Inhibitors
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Mycotoxins
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Oligopeptides
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Peptide Fragments
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Protein Kinase Inhibitors
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Teratogens
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Xanthenes
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Xanthones
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secalonic acid
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kemptide
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Cyclic AMP-Dependent Protein Kinases
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Protein Kinase C
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Myosin-Light-Chain Kinase