Bignon E, Ogita K, Kishimoto A, Gilbert J, Abecassis J, Miquel J F, Nishizuka Y
Department of Biochemistry, Kobe University School of Medicine, Japan.
Biochem Biophys Res Commun. 1989 Sep 29;163(3):1377-83. doi: 10.1016/0006-291x(89)91131-5.
Protein kinase C (PKC) I (gamma), II (beta) and III (alpha) subspecies' activities are inhibited by three triphenylacrylonitrile (TPE) antiestrogens at micromolar concentrations. TPE 1 (having a p-hydroxy and a p-diethylaminoethoxy group on the 3-, and 3'- phenyl rings respectively) and TPE 2 (having a p-diethylaminoethoxy group on both the 3-, and 3'- phenyl rings) are competitive with the mechanism of activation by phosphatidylserine (PS). TPE 3 (having p-hydroxy groups on each of the three phenyl rings) is non-competitive with PS and inhibits the Ca2+- and PS-independent phosphorylation of protamine sulfate by PKC subspecies. This evidence suggests that PKC activity can be inhibited by different routes depending on the TPE structure: diethylaminoethoxy side chain-substituted TPEs (TPE 1 and 2) interact with PS as well as with the regulatory domain, whereas the trihydroxylated derivative (TPE 3) inhibits the enzyme by interacting with the catalytically active site.
蛋白激酶C（PKC）的I（γ）、II（β）和III（α）亚型的活性在微摩尔浓度下会被三种三苯丙烯腈（TPE）抗雌激素所抑制。TPE 1（在3-和3'-苯环上分别有一个对羟基和一个对二乙氨基乙氧基）和TPE 2（在3-和3'-苯环上均有一个对二乙氨基乙氧基）与磷脂酰丝氨酸（PS）的激活机制存在竞争性。TPE 3（在三个苯环上各有一个对羟基）与PS不存在竞争性，并抑制PKC亚型对硫酸鱼精蛋白的Ca2+和PS非依赖性磷酸化。这一证据表明，根据TPE的结构，PKC的活性可以通过不同途径被抑制：二乙氨基乙氧基侧链取代的TPE（TPE 1和TPE 2）与PS以及调节结构域相互作用，而三羟基化衍生物（TPE 3）通过与催化活性位点相互作用来抑制该酶。
