Kinetics of regulatory serine variants of tyrosine hydroxylase with cyclic AMP-dependent protein kinase and extracellular signal-regulated protein kinase 2.
Kinetics of regulatory serine variants of tyrosine hydroxylase with cyclic AMP-dependent protein kinase and extracellular signal-regulated protein kinase 2.
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酪氨酸羟化酶调节丝氨酸变体与环 AMP 依赖性蛋白激酶和细胞外信号调节蛋白激酶 2 的动力学。
DOI：
10.1016/j.bbapap.2006.01.019
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
ColetteDaubner,S
中科院分区：
文献类型：
--
作者：
Royo,Montserrat;ColetteDaubner,S
大鼠酪氨酸羟化酶在其氨基末端调节结构域的8、19、31和40位的四个丝氨酸残基处被多种蛋白激酶磷酸化。环腺苷酸依赖性蛋白激酶磷酸化S40，从而减轻多巴胺的抑制作用。细胞外信号调节蛋白激酶2磷酸化S8和S31。将定点丝氨酸-谷氨酸突变引入酪氨酸羟化酶以模拟先前的调节丝氨酸磷酸化;这些蛋白质用作cAMP依赖性激酶和细胞外信号调节激酶2的底物。cAMP依赖性激酶的活性不受丝氨酸8、19或31被谷氨酸取代的影响，细胞外信号调节激酶2的活性不受丝氨酸19或40被谷氨酸取代的影响。如果多巴胺与酪氨酸羟化酶结合，则环腺苷酸依赖性激酶在磷酸化S40中活性较低，但细胞外信号调节激酶2在S31的磷酸化不受多巴胺的影响。
Rat tyrosine hydroxylase is phosphorylated at four serine residues, at positions 8, 19, 31, and 40 in its amino terminal regulatory domain by multiple protein kinases. Cyclic AMP-dependent protein kinase phosphorylates S40, which results in alleviation of inhibition by dopamine. Extracellular signal-regulated protein kinase 2 phosphorylates S8 and S31. Site-directed serine-to-glutamate mutations were introduced into tyrosine hydroxylase to mimic prior phosphorylation of the regulatory serines; these proteins were used as substrates for cAMP-dependent kinase and extracellular signal-regulated kinase 2. The activity of cAMP-dependent kinase was unaffected by the substitution of serines 8, 19 or 31 with glutamate and the activity of extracellular signal-regulated kinase 2 was unaffected by substitution of serines 19 or 40 with glutamate. Cyclic AMP-dependent kinase was less active in phosphorylating S40 if dopamine was bound to tyrosine hydroxylase, but extracellular signal-regulated kinase 2 phosphorylation at S31 was unaffected by the presence of dopamine.