Methylation of Smad6 by protein arginine N-methyltransferase 1
Methylation of Smad6 by protein arginine N-methyltransferase 1
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DOI：
10.1016/j.febslet.2006.11.008
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发表时间：
2006-12-11
期刊：
影响因子：
3.5
通讯作者：
Kato, Mitsuyasu
中科院分区：
文献类型：
--
作者：
Inamitsu, Masako;Itoh, Susumu;Kato, Mitsuyasu
信号转导通路利用翻译后修饰以时间-空间和有效的方式调节其组成部分的活性。精氨酸甲基化是一种翻译后修饰，可导致蛋白质中的单甲基化、不对称双甲基化和/或对称双甲基化精氨酸残基。在这里，我们证明了抑制性Smads(Smad6和Smad7)，而不是受体调节的(R-)Smads和共同伙伴Smad4，可以被精氨酸N-甲基转移酶(PRMT)1甲基化。利用质谱分析，我们发现PRMT1在小鼠Smad6中二甲基化精氨酸(74)(Arg(74))。PRMT1与Arg(74)残基所在的Smad6的N-末端结构域相互作用。到目前为止，检测表明Smad6和甲基化缺陷Smad6(Smad6R74A)的功能没有显著差异。野生型和Smad6R74A在HS-72小鼠B细胞杂交瘤细胞中的异位表达同样有效地阻断了BMP诱导的生长停滞。(C)2006年欧洲生化学会联合会。爱思唯尔出版，版权所有。
Signal transduction pathways utilize posttranslational modifications to regulate the activity of their components in a temporal-spatial and efficient fashion. Arginine methylation is one of the posttranslational modifications that can result in monomethylated-, asymmetric dimethylated- and/or symmetric dimethylated-arginine residues in proteins. Here we demonstrate that inhibitory-Smads (Smad6 and Smad7), but not receptor-regulated- (R-)Smads and the common-partner Smad4, can be methylated by protein arginine N-methyltransferase (PRMT)1. Using mass-spectrometric analysis, we found that PRMT1 dimethylates arginine(74) (Arg(74)) in mouse Smad6. PRMT1 interacts with the N-terminal domain of Smad6 in which Arg(74) residue is located. Assays examined so far have shown no significant differences between the functions of Smad6 and those of methylation-defective Smad6 (Smad6R74A). Both wild-type and Smad6R74A were equally efficient in blocking BMP-induced growth arrest upon their ectopic expression in HS-72 mouse B-cell hybridoma cells. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.