Peptide substrates for ERK1/2: structure-function studies of serine 31 in tyrosine hydroxylase
Peptide substrates for ERK1/2: structure-function studies of serine 31 in tyrosine hydroxylase
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DOI：
10.1016/s0165-0270(02)00025-0
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发表时间：
2002-04-30
影响因子：
3
通讯作者：
Haycock, JW
中科院分区：
文献类型：
--
作者：
Haycock, JW
细胞外信号调节蛋白激酶(ERKs)的第一个生理底物是酪氨酸羟基酶(TH)中的丝氨酸31，它是儿茶酚胺生物合成的限速酶。在本研究中，几个模拟TH中Ser31的合成肽被评估为ERKs的体外底物。重组ERK2被激活的重组ERK2磷酸化人类1型TH中含Ser31的多肽，其催化效率(V-max/K-m)比合成的髓鞘碱性蛋白(MBP)多肽高4倍。这两种类型的多肽也用PC12细胞的提取物(未处理或用神经生长因子(NGF)处理)进行了测试。尽管PC12细胞提取物对MBP多肽的磷酸化程度高于Ser31多肽，但Ser31多肽的相对磷酸化程度更大，且更接近ERK的磷酸化模式，提示后者可能是ERKs更特异的底物。(C)2002 Elsevier Science B.V.保留所有权利。
The first physiological substrate identified for the extracellular signal-regulated protein kinases (ERKs) is serine 31 in tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis. In the present studies, several synthetic peptides modeled after Ser31 in TH were evaluated as in vitro substrates for the ERKs. The phosphorylation of Ser31-containing peptides from type 1 human TH by activated, recombinant ERK2 was found to exhibit catalytic efficiencies (V-max/K-m) up to 4-fold higher than that of a synthetic myelin basic protein (MBP)-based peptide. Both types of peptides were also tested using extracts from PC12 cells (untreated or treated with nerve growth factor (NGF)). Although, the phosphorylation of the MBP peptide by extracts of PC12 cells was higher than that of the Ser31 peptide, the relative treatment-dependent increase was much greater for the Ser31 peptide and more closely mimicked the pattern of ERK phosphorylation, suggesting that the latter peptide may be a more specific substrate for the ERKs. (C) 2002 Elsevier Science B.V. All rights reserved.