Effect of tamoxifen, a nonsteroidal antiestrogen, on phospholipid/calcium-dependent protein kinase and phosphorylation of its endogenous substrate proteins from the rat brain and ovary.
Effect of tamoxifen, a nonsteroidal antiestrogen, on phospholipid/calcium-dependent protein kinase and phosphorylation of its endogenous substrate proteins from the rat brain and ovary.
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DOI：
10.1016/0006-2952(85)90225-4
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发表时间：
1985-10
影响因子：
5.8
通讯作者：
H. Su;G. Mazzei;W. Vogler;J. Kuo
中科院分区：
文献类型：
--
作者：
H. Su;G. Mazzei;W. Vogler;J. Kuo
发现抗雌激素（他莫昔芬、克罗米芬和萘福昔定）抑制磷脂/Ca2+依赖性蛋白激酶（PL/Ca-PK）。或蛋白激酶C）。而雌激素（雌二醇和己烯雌酚）和弱雌激素性的氯三茴香醚是无活性的。动力学分析表明，抗雌激素对磷脂酰丝氨酸具有竞争性抑制作用（Ki = 16 - 27，μ M），而对Ca~（2+）具有非竞争性抑制作用（Ki = 14 - 30 μ M）。他莫昔芬，但不是己烯雌酚，也抑制磷脂/Ca2+依赖性磷酸化的各种内源性蛋白质从总的，溶解部分的大鼠大脑和卵巢。肌球蛋白轻链激酶，钙调蛋白/Ca2+依赖类蛋白激酶，同样抑制他莫昔芬：药物，但是，是没有影响环AMP依赖性和环GMP依赖性蛋白激酶。有人建议，PL/Ca-PK，凭借所需的酶激活的疏水相互作用，可能代表一个潜在的亲脂性抗雌激素的作用位点，除了公认的细胞内雌激素受体。
Antiestrogens (tamoxifen, clomiphene and nafoxidine) were found to inhibit phospholipid/ Ca2+-dependent protein kinase (PL/Ca-PK. or protein kinase C). whereas estrogens (estradiol and diethylstilbesterol) and the weakly estrogenic chlorotrianisene were inactive. Kinetic analysis indicated that the antiestrogens inhibited PL/Ca-PK competitively with respect to phosphatidylserine (Ki= 16–27,μM), but non-competitively with Ca2+(Ki= 14–30μM). Tamoxifen, hut not diethylstilbesterol, also inhibited the phospholipid/Ca2+-dependent phosphorylation of various endogenous proteins from the total, solubilized fraction of the rat brain and ovary. Myosin light chain kinase, a calmodulin/Ca2+-dependent class of protein kinase, was similarly inhibited by tamoxifen: the drug, however, was without effect on cyclic AMP-dependent and cyclic GMP-dependent protein kinases. It is suggested that PL/ Ca-PK, by virtue of the hydrophobic interactions required for the enzyme activation, may represent a potential site of action for the lipophilic antiestrogens, in addition to the commonly recognized intracellular estrogen receptors.