Huang C F, Tong J, Schmidt J
Department of Biochemistry and Cell Biology, State University of New York, Stony Brook 11794.
Neuron. 1992 Oct;9(4):671-8. doi: 10.1016/0896-6273(92)90030-h.
The signaling pathway connecting membrane depolarization and gene activity in skeletal muscle remains largely unknown. Using transcription elongation (run-on) analysis we have found that electrical stimulation of denervated chick skeletal muscle in vivo rapidly and selectively results in inactivation of acetylcholine receptor (AChR) subunit genes. We have studied the possible involvement of protein kinase C (PKC) in this response and have observed that electrical stimulation increases the activity of PKC in the nucleus by over two orders of magnitude within 10 min; phorbol esters, within minutes after intramuscular application, block AChR subunit genes in the absence of electrical activity; and the activity-triggered gene inactivation is blocked by the protein kinase inhibitor staurosporine or by enzyme depletion resulting from chronic pretreatment of muscle with phorbol esters. We conclude that PKC is an integral component of the pathway coupling membrane excitation and AChR gene control.
连接膜去极化与骨骼肌基因活性的信号通路在很大程度上仍不为人知。通过转录延伸（连续转录）分析，我们发现体内对去神经支配的鸡骨骼肌进行电刺激会迅速且选择性地导致乙酰胆碱受体（AChR）亚基基因失活。我们研究了蛋白激酶C（PKC）在这一反应中可能的作用，观察到电刺激在10分钟内使细胞核内PKC的活性增加了两个数量级以上；肌肉内注射佛波酯后几分钟内，在无电活动的情况下阻断AChR亚基基因；蛋白激酶抑制剂星形孢菌素或因用佛波酯对肌肉进行长期预处理导致的酶耗竭可阻断活性触发的基因失活。我们得出结论，PKC是连接膜兴奋与AChR基因调控通路的一个不可或缺的组成部分。
