Characterization of (-)-matairesinol as a potent inhibitor of casein kinase I in vitro.
The inhibitory effects of (-)-matairesinol (MTS) isolated from Thujopsis dolabrata var. hondai on the activities of four distinct Ser/Thr-protein kinases [two casein kinases (CK-I and CK-II), A-kinase and C-kinase] were determined in vitro. It was found that (i) MTS inhibits the activities of CK-I and C-kinase alpha (ID(50)=approx. 10 microM) in a dose-depedent manner, but high doses are required to inhibit A-kinase activity (ID(50)=approx. 90 microM); (ii) the autophosphorylation of CK-I is more sensitive to MTS (ID(50)=approx. 0.2 microM); (iii) MTS inhibits CK-I activity in a manner similar to that observed with CK-I-7 (a CK-I inhibitor); and (iv) the compound inhibits CK-I activity by affecting ATP binding in a mixed type manner. These results indicate that MTS is a potent CK-I inhibitor in vitro.
Yokoyama
Takamasa
T
Genetical Biochemistry, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Japan.
Okano
Maiko
M
Noshita
Toshiro
T
Funayama
Shinji
S
Ohtsuki
Kenzo
K
D001345:Autoradiography / Q000379:methods; D047388:Casein Kinases; D003402:Creatine Kinase / Q000145:classification / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005663:Furans / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D017705:Lignans / Q000494:pharmacology*; D010759:Phosphorus Isotopes / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000145:classification / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D013379:Substrate Specificity
D004791:Enzyme Inhibitors; D005663:Furans; D017705:Lignans; D010759:Phosphorus Isotopes; D047428:Protein Kinase Inhibitors; C068935:matairesinol; D011494:Protein Kinases; D047388:Casein Kinases; D017346:Protein Serine-Threonine Kinases; D003402:Creatine Kinase