The Fungal Teratogen Secalonic Acid D is an Inhibitor of Protein Kinase C and of Cyclic AMP-Dependent Protein Kinase

Abstract

The teratogenic metabolite secalonic acid D deriving from the ergot-producing, rye-infecting ascomycete fungus Claviceps purpurea and from Penicillium 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) (IC₅₀ values 15 µM and 12 µM, 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.

Key words

Protein kinase inhibitors - Claviceps purpurea - Penicillium oxalicum - Ascomycotina - Secale cereale - Poaceae - secalonic acid D - teratogens