Biochemical analysis of the arginine methylation of high molecular weight fibroblast growth factor-2
Biochemical analysis of the arginine methylation of high molecular weight fibroblast growth factor-2
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DOI：
10.1074/jbc.275.5.3150
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发表时间：
2000-02-04
影响因子：
4.8
通讯作者：
Rifkin, DB
中科院分区：
文献类型：
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作者：
Klein, S;Carroll, JA;Rifkin, DB
成纤维细胞生长因子-2 （FGF-2）的n端延伸或高分子量（HMW）形式的翻译后甲基化已被证明会影响生长因子的核积累。在这项研究中，我们确定了甲基在HMW FGF-2中的范围和位置。通过质谱分析和氨基酸序列分析，我们发现HMW FGF-2的22和22.5 kda形式含有5个二甲基化精氨酸，位于-22、-24、-26、-36和-38位，通常用于启动18 kda形式的蛋氨酸残基为0位。24kda形式的HMW FGF-2除了-22、-24、-26、-36和-38位点外，还含有7到8个位于-48、-50和-52位点的二甲基化精氨酸。体外甲基化反应表明，HMW FGF-8的n端延伸作为酵母Hmt1p和人hrmtt1l2精氨酸甲基转移酶的特定底物。这些发现表明，HMW FGF-8具有5个或更多的二甲基化Gly-Arg-Gly重复序列，包含RGG盒状结构域，这可能对蛋白质-蛋白质和/或蛋白质- rna相互作用很重要。
The post-translational methylation of the N-terminally extended or high molecular weight (HMW) forms of fibroblast growth factor-2 (FGF-2) has been shown to affect the nuclear accumulation of the growth factor. In this study, we determined the extent and position of methyl groups in HMW FGF-2. Using mass spectrometry and amino acid sequence analysis, we have shown that the 22- and 22.5-kDa forms of HMW FGF-2 contain five dimethylated arginines located at positions -22, -24, -26, -36, and -38 using the methionine residue normally used to initiate the 18-kDa form as position 0. The 24-kDa form of HMW FGF-2 contains seven to eight dimethylated arginines located at positions -48, -50, and -52, in addition to positions -22, -24, -26, -36, and -38, In vitro methylation reactions demonstrate that the N-terminal extension of HMW FGF-8 acts as a specific substrate for yeast Hmt1p and human HRMT1L2 arginine methyltransferases. These findings indicate that HMW FGF-8, with the presence of five or more dimethylated Gly-Arg-Gly repeats, contains an RGG box-like domain, which may be important for protein-protein and/or protein-RNA interactions.