ACTIVATION OF PROTEIN KINASE-C BY TUMOR PROMOTING PHORBOL ESTERS, TELEOCIDIN AND APLYSIATOXIN IN THE ABSENCE OF ADDED CALCIUM
ACTIVATION OF PROTEIN KINASE-C BY TUMOR PROMOTING PHORBOL ESTERS, TELEOCIDIN AND APLYSIATOXIN IN THE ABSENCE OF ADDED CALCIUM
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DOI：
10.1093/carcin/6.2.213
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发表时间：
1985-01-01
期刊：
影响因子：
4.7
通讯作者：
WEINSTEIN, IB
中科院分区：
文献类型：
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作者：
ARCOLEO, JP;WEINSTEIN, IB
12-O-十四酰基佛波醇-13-乙酸酯（TPA）对牛脑制备的钙和磷脂依赖性蛋白激酶（PKC）的激酶活性的最大刺激（> 10倍）发生在磷脂存在但不存在添加的Ca 2+的情况下。实际上，nM浓度的TPA替代了mM浓度的添加的Ca 2 +;这2种试剂不具有协同作用。TPA的生物活性类似物如佛波醇-12，13-二丁酸酯（PDBu）、12-O-十六酰基-16-羟基佛波醇-13-乙酸酯（HHPA）或mezerein也是PKC的有效激活剂，当在不存在添加的Ca 2+的情况下以nM浓度测试时，化学上不相关的肿瘤促进剂teleocidin和aperosiatoxin也是PKC的有效激活剂。生物学上无活性的化合物佛波醇，4-α-佛波醇-12，13-二癸酸酯（4-α- PDD）、HHPA-13，20-diacetate和1，2-dihydro-20-deoxy-HHPA在无Ca ~（2+）或有Ca ~（2+）存在时均不影响PKC活性。这些结果是一致的立体化学模型，其中某些二萜类，teleocidin和aperossiatoxin的亲水结构域相互作用，特别是与PKC脱辅基酶，而它们的疏水结构域与磷脂相互作用，从而形成一个酶活性的三元复合物。
Maximum stimulation (> 10-fold) of kinase activity of a bovine brain preparation of Ca- and phospholipid-dependent protein kinase (PKC) by 12-O-tetradecanoylphorbol-13-acetate (TPA) occurs in the presence of phospholipid, but in the absence of added Ca2+. In effect, nM concentrations of TPA substitute for mM concentrations of added Ca2+; the 2 agents are not synergistic. Biologically active analogs of TPA such as phorbol-12,13-dibutyrate (PDBu), 12-O-hexadecanoyl-16-hydroxyphorbol-13-acetate (HHPA) or mezerein were also effective activators of PKC, as were the chemically unrelated tumor promoters teleocidin and aplysiatoxin, when tested at nM concentrations in the absence of added Ca2+. The biologically inactive compounds phorbol, 4-.alpha.-phorbol-12,13-didecanoate (4-.alpha.-PDD), HHPA-13,20-diacetate and 1,2-dihydro-20-deoxy-HHPA did not affect PKC activity in the absence or presence of Ca2+. These results are consistent with a stereochemical model in which the hydrophilic domains of certain diterpenes, teleocidin and aplysiatoxin interact specifically with PKC apoenzyme, while their hydrophobic domains interact with phospholipid, thus forming an enzymatically active ternary complex.