A bryostatin-sensitive protein kinase C required for nerve growth factor activity.
A bryostatin-sensitive protein kinase C required for nerve growth factor activity.
复制标题
神经生长因子活性所需的苔藓抑素敏感蛋白激酶 C。
DOI：
10.1021/bi00168a020
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发表时间：
1994
期刊：
影响因子：
2.9
通讯作者：
Neet,KE
中科院分区：
文献类型：
--
作者：
Singh,KR;Taylor,LK;Campbell,XZ;Fields,AP;Neet,KE
修订稿于 1993 年 10 月 4 日收到• 摘要：神经生长因子 (NGF) 刺激大鼠嗜铬细胞瘤细胞 (PC 12) 分化为具有神经突延伸的神经元样细胞。蛋白激酶 C 在信号转导中的作用已在用佛波醇 12-肉豆蔻酸酯 13-乙酸酯 (PMA) 和苔藓抑素处理的 PC 12 细胞中进行了检查，苔藓抑素是一种大环内酯，可激活核膜和质膜上的蛋白激酶 Cat [Hocevar, B. A., & Fields, A. P.(1991) J. Biol.化学。 266、28-33]。与 PMA 下调相反 [Reinhold, D. S., & Neet, K. E.(1989) J. Biol.化学。 [264, 3538-3544]，用苔藓抑素长期（24小时）治疗可阻断响应 NGF 或碱性成纤维细胞衍生生长因子刺激的神经突形成，但与 PMA 一样，苔藓抑素并不能阻断 NGF 对 c-fos 或 c-jun 原癌基因的诱导。长期苔藓抑素治疗可下调细胞质、膜和核部分中的蛋白激酶 C 活性。急性（60 分钟）苔藓抑素或 NGF 处理激活胞质和核蛋白激酶 C 活性，表明可能易位至细胞核。无论是单独使用还是与 PMA 联合使用，苔藓抑素均不会诱导神经突生长。因此，苔藓抑素敏感蛋白激酶 C 不同于先前描述的 PMA 或 K252a 敏感激酶。苔藓抑素敏感的蛋白激酶 C 对于神经突的生长是必要的，但不是充分的，并且以独立于 c-fos 和 c-jun 转录的方式在细胞核中起作用。神经生长因子 (NGF) 1 在脊椎动物神经元的发育和维持中发挥作用（Levi-Montalcini & Angeletti, 1968; Greene & Shooter, 1980; Yankner & Shooter, 1982;列维-蒙塔尔奇尼，1987）。大鼠嗜铬细胞瘤细胞系 PC 12 (Greene & Tischler, 1976) 对 NGF 有反应
Revised Manuscript Received October 4, 1993• abstract: Nerve growth factor (NGF) stimulates rat pheochromocytoma cells (PC 12) to differentiate into a neuronal-like cell that exhibits neurite extensions. The role of protein kinase C in signal transduction has been examined in PC 12 cells treated with phorbol 12-myristate 13-acetate (PMA) and bryostatin, a macrocyclic lactone that activates protein kinase Cat both the nuclear and the plasma membranes [Hocevar, B. A., & Fields, A. P.(1991) J. Biol. Chem. 266, 28-33]. In contrast to PMA down-regulation [Reinhold, D. S., & Neet, K. E.(1989) J. Biol. Chem. 264, 3538-3544], chronic (24 h) treatment with bryostatin blocked the formation of neurites in response to NGF or basic fibroblast-derived growth factor stimulation, but, like PMA, bryostatindid not block the induction of c-fos or c-jun protooncogenes by NGF. Chronic bryostatin treatment down-regulated protein kinase C activity in the cytosolic, membrane, and nuclear fractions. Acute (60 min) bryostatin or NGF treatment activated cytosolic and nuclear protein kinase C activity, suggesting possible translocation to the nucleus. Bryostatin did not induce neurite outgrowth, either alone or in combination with PMA. Thus, the bryostatin-sensitive protein kinase C is distinct from PMA-or K252a-sensitive kinases previously described. The bryostatin-sensitive protein kinase C is necessary, but not sufficient, for neurite outgrowth andacts in the nucleus in a manner independent of c-fos and c-jun transcription.Nerve growth factor (NGF) 1 plays a role in the development and maintenance of vertebrate neurons(Levi-Montalcini & Angeletti, 1968; Greene & Shooter, 1980; Yankner & Shooter, 1982; Levi-Montalcini, 1987). The rat pheochromocytoma cell line PC 12 (Greene & Tischler, 1976) responds to NGF