Yuanhuacin A is a selective antagonist of phorbol ester receptor in protein kinase C.
Protein kinase C with a molecular weight of 82 kD has been purified to electrophoresis homogeneous from rat brain through a series of chromatography columns including DE-52, Sepharose G-200 and phenyl-Sepharose. The enzyme possessed autophosphorylation activity. Yuanhuacin A inhibited the 3H-phorbol-12, 13-dibutyrate (3H-PdBu) binding of PKC with an IC50 value of 1.48 +/- 0.28 x 10(-8) mol/L when the concentration of 3H-PdBu was 1.5 x 10(-9) mol/L (Ki = 1.2 x 10(-8) mol/L). Yuanhuacin A inhibited the PdBu-stimulated PKC activity in the catalysis of the phosphorylation of Histone III-S with an IC50 of 2.82 +/- 0.37 x 10(-9) mol/L (PdBu = 10(-6) mol/L), while it had no effect on the basal and Ca(2+)-stimulated PKC activity in the same assay system. This result suggests that Yuanhuacin A is a selective antagonist of the phorbol ester receptor in protein kinase C.
Zhang
D C
DC
Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing.
Cao
C X
CX
Zhang
C J
CJ
Zhou
B N
BN
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D004224:Diterpenes / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D008297:Male; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000037:antagonists & inhibitors*
D000972:Antineoplastic Agents, Phytogenic; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D011955:Receptors, Drug; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; D015240:Phorbol 12,13-Dibutyrate; C029912:Yuanhuacin; D011493:Protein Kinase C