The School of Biomedical Sciences and Pharmacy and The Hunter Medical Research Institute, The University of Newcastle, University Drive, Callaghan, NSW, Australia.
J Neurochem. 2019 Jun;149(6):706-728. doi: 10.1111/jnc.14675. Epub 2019 Mar 20.
Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the synthesis of the catecholamines dopamine, noradrenaline and adrenaline. One of the major mechanisms for controlling the activity of TH is protein phosphorylation. TH is phosphorylated at serine residues 8, 19, 31 and 40. There have been a number of previous reviews focused on TH phosphorylation in vitro and in situ. This review on TH phosphorylation in vivo has three main sections focusing on: (1) the methods used to investigate TH phosphorylation in vivo, including the animals used, the sacrifice procedures, the tissue preparation, the measurement of TH protein levels and TH phosphorylation and the measurement of TH activation. (2) The regulation of TH phosphorylation and its consequences in vivo, including the kinases and phosphatases acting on TH, the stoichiometry of TH phosphorylation, the proteins that bind TH and TH subcellular location. (3) The acute and prolonged TH phosphorylation changes in specific catecholaminergic tissues, including the adrenal medulla, the nigrostriatal pathway and the mesolimbic pathway.
酪氨酸羟化酶（TH）是儿茶酚胺（多巴胺、去甲肾上腺素和肾上腺素）合成中的限速酶。控制 TH 活性的主要机制之一是蛋白质磷酸化。TH 在丝氨酸残基 8、19、31 和 40 处发生磷酸化。之前有许多专注于 TH 体外和原位磷酸化的综述。本综述重点关注体内 TH 磷酸化，主要分为三个部分：（1）用于研究体内 TH 磷酸化的方法，包括所用动物、处死程序、组织准备、TH 蛋白水平和 TH 磷酸化的测量以及 TH 活性的测量。（2）体内 TH 磷酸化的调节及其后果，包括作用于 TH 的激酶和磷酸酶、TH 磷酸化的化学计量、与 TH 结合的蛋白质和 TH 的亚细胞定位。（3）特定儿茶酚胺能组织中急性和长期的 TH 磷酸化变化，包括肾上腺髓质、黑质纹状体通路和中脑边缘通路。
