Griffiths J, Marley P D
Department of Pharmacology, University of Melbourne, Victoria 3010, Australia.
Neuroreport. 2001 Aug 28;12(12):2679-83. doi: 10.1097/00001756-200108280-00018.
Tyrosine hydroxylase (TOH) activity is regulated acutely by phosphorylation of serines 8, 19, 31 and 40. The only kinases known to phosphorylate Ser31 are the mitogen-activated protein kinases MAPK-1 and 2. The involvement of these kinases in TOH activation in situ was therefore investigated using intact bovine chromaffin cells. Nicotine, K+ and A23187 increased TOH activity over 10 min in a Ca2+-dependent manner. The response to all three was reduced by PD098059, a selective inhibitor of the upstream activator of MAPK, MEK1. In contrast, TOH activation by forskolin and phorbol dibutyrate were unaffected by PD098059. The results support a key role for MEK1/MAPK in the acute activation of TOH by nicotinic receptors and by other agonists that increase cytosolic Ca2+.
酪氨酸羟化酶（TOH）的活性通过丝氨酸8、19、31和40的磷酸化受到急性调节。已知唯一能使Ser31磷酸化的激酶是丝裂原活化蛋白激酶MAPK-1和2。因此，使用完整的牛嗜铬细胞研究了这些激酶在原位TOH激活中的作用。尼古丁、K⁺和A23187在10分钟内以Ca²⁺依赖的方式增加了TOH的活性。PD098059是MAPK上游激活剂MEK1的选择性抑制剂，它降低了对所有这三种物质的反应。相比之下，福斯高林和佛波醇二丁酸酯对TOH的激活不受PD098059的影响。这些结果支持了MEK1/MAPK在烟碱受体以及其他增加胞质Ca²⁺的激动剂对TOH的急性激活中起关键作用。
