Szallasi Z, Smith C B, Pettit G R, Blumberg P M
Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892.
J Biol Chem. 1994 Jan 21;269(3):2118-24.
Bryostatin 1 and phorbol 12-myristate 13-acetate (PMA) are both potent activators of protein kinase C (PKC), although in many systems bryostatin 1 induces only a subset of the responses to PMA and blocks those which it does not induce. We report here that in NIH 3T3 fibroblasts PMA showed similar potencies for translocating PKC isozymes alpha, delta, and epsilon to the Triton X-100-soluble and -insoluble fractions and for the down-regulation of the three isozymes. Bryostatin 1 was slightly was more potent than PMA for down-regulating it. Bryostatin 1 was markedly more potent than PMA for translocating PKC delta but showed a biphasic dose-response curve for down-regulating this isozyme. 1-10 nM bryostatin 1 down-regulated PKC delta to a similar extent as PMA; lower (10-100 pM) or, unexpectedly, higher (100 nM to 1 microM) doses of bryostatin 1 caused either no or reduced down-regulation. Moreover, these high (100 nM to 1 microM) doses of bryostatin 1 inhibited the down-regulation of PKC delta by 1 microM PMA when coapplied. Bryostatin 1 caused translocation of PKC epsilon with slightly higher potency than PKC delta, but there was no protection of this isozyme at any of the doses examined. Bryostatin 1 induced a long-term increase in c-Jun level. The dose-response curve for bryostatin 1 was biphasic, with maximal induction at 1-10 nM bryostatin 1, coincident with the maximal down-regulation of PKC delta. We conclude that bryostatin 1 showed substantially different regulation for PKC alpha, PKC delta, and PKC epsilon, whereas PMA distinguished only weakly between these isozymes.
苔藓抑素1和佛波醇12 -肉豆蔻酸酯13 -乙酸酯（PMA）都是蛋白激酶C（PKC）的有效激活剂，尽管在许多系统中，苔藓抑素1仅诱导对PMA反应的一个子集，并阻断那些它不诱导的反应。我们在此报告，在NIH 3T3成纤维细胞中，PMA在将PKC同工酶α、δ和ε转运至 Triton X - 100可溶和不可溶部分以及下调这三种同工酶方面表现出相似的效力。苔藓抑素1在下调PKC方面比PMA稍强。苔藓抑素1在转运PKCδ方面比PMA明显更强，但在下调这种同工酶方面呈现双相剂量反应曲线。1 - 10 nM苔藓抑素1下调PKCδ的程度与PMA相似；较低（10 - 100 pM）或出乎意料的是较高（100 nM至1 μM）剂量的苔藓抑素1导致下调不明显或下调减少。此外，这些高（100 nM至1 μM）剂量的苔藓抑素1在共同应用时会抑制1 μM PMA对PKCδ的下调。苔藓抑素1导致PKCε的转位，效力略高于PKCδ，但在所检测的任何剂量下对这种同工酶均无保护作用。苔藓抑素1诱导c - Jun水平长期升高。苔藓抑素1的剂量反应曲线是双相的，在1 - 10 nM苔藓抑素1时诱导最大，这与PKCδ的最大下调一致。我们得出结论，苔藓抑素1对PKCα、PKCδ和PKCε表现出显著不同的调节作用，而PMA在这些同工酶之间的区分较弱。
