A new type of protein methylation activated by tyrphostin A25 and vanadate
A new type of protein methylation activated by tyrphostin A25 and vanadate
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DOI：
10.1016/j.febslet.2004.09.080
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发表时间：
2004-11-05
期刊：
影响因子：
3.5
通讯作者：
Clarke, S
中科院分区：
文献类型：
--
作者：
Miranda, TB;Lowenson, JD;Clarke, S
已有报道，酪氨酸激酶抑制剂tyrphostin A25可显著刺激大鼠肾提取物中S-腺苷甲硫氨酸依赖的蛋白质甲基化。我们已经研究了这种刺激的性质。我们发现，除了酪氨酸磷酸酶抑制剂A25，与蛋白磷酸酶抑制剂钒酸盐，导致刺激的64，42，40，36，31，和15 kDa的多肽在小鼠肾脏的胞质提取物的甲基化。酪氨酸磷酸化抑制剂的作用似乎对A25物种具有相对特异性。增强的甲基化并不代表蛋白质组氨酸、赖氨酸或精氨酸甲基转移酶家族的活性，也不代表L-异戊酰基/D-戊酰基甲基转移酶的活性，这些酶在大多数细胞类型中负责大量蛋白质甲基化。甲基化多肽的化学和酶分析表明，甲基是在酯键的蛋白质。在心脏提取物中，我们发现了类似的情况，但是在这里甲基化的刺激不依赖于钒酸盐，并且发现了另外的18 kDa甲基化物质。这项工作为一种新型的蛋白质羧基甲基化反应提供了证据，这种反应可能在某些哺乳动物组织的信号反应中发挥作用。(C)2004年由Elsevier B. V.代表欧洲生物化学学会联合会出版。
It has been reported that S-adenosylmethionine-dependent protein methylation in rat kidney extracts can be greatly stimulated by tyrphostin A25, a tyrosine kinase inhibitor. We have investigated the nature of this stimulation. We find that addition of tyrphostin A25, in combination with the protein phosphatase inhibitor vanadate, leads to the stimulation of methylation of polypeptides of 64, 42, 40, 36, 31, and 15 kDa in cytosolic extracts of mouse kidney. The effect of tyrphostin appears to be relatively specific for the A25 species. The enhanced methylation does not represent the activity of the families of protein histidine, lysine or arginine methyltransferases, nor that of the L-isoaspartyl/D-aspartyl methyltransferase, enzymes responsible for the bulk of protein methylation in most cell types. Chemical and enzymatic analyses of the methylated polypeptides suggest that the methyl group is in an ester linkage to the protein. In heart extracts, we find a similar situation but here the stimulation of methylation is not dependent upon vanadate and an additional 18 kDa methylated species is found. In contrast, little or no stimulation of methylation is found in brain or testis extracts. This work provides evidence for a novel type of protein carboxyl methylation reaction that may play a role in signaling reactions in certain mammalian tissues. (C) 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.