1H, 15N, 13C resonance assignments of the human protein tyrosine phosphatase PRL-1.
1H, 15N, 13C resonance assignments of the human protein tyrosine phosphatase PRL-1.
复制标题
人蛋白酪氨酸磷酸酶 PRL-1 的 1H、15N、13C 共振归属。
DOI：
10.1023/b:jnmr.0000032506.16792.c6
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发表时间：
2004
影响因子：
2.7
通讯作者：
Stauffacher,CynthiaV
中科院分区：
文献类型：
--
作者：
Laurence,JenniferS;Hallenga,Klaas;Stauffacher,CynthiaV
由于PRL酶参与转移性癌症，因此它们已成为药物设计的高度追捧的靶标。PRL-1和PRL-3的水平升高已显示触发转移，并且PRL-1和PRL-2促进细胞转化和肿瘤发生（Zeng等人，2003; Saha等人，2001; Cates等人，1996年）。PRL-1最初被鉴定为参与大鼠部分肝切除术后肝再生的早期应答基因（Diamond等人，1994年）。PRL酶仅在多细胞真核生物中发现。在哺乳动物中存在三种亚型，C.线虫和果蝇似乎各有一个同源物。PRL的区别特征是它们的C-末端CaaX基序，其指导Cys的法尼基化（Zeng et al.，2000年）。通过蛋白水解两个脂肪族残基（aa）和额外的C-末端残基（X），以及通过新的C-末端法尼基-Cys的α-羧基甲基化，可以进一步改变修饰的蛋白质（Clarke，1992）。此外，PRL磷酸酶在C端编码一个高碱性区域，该区域可能作为核定位信号或次级膜结合基序，这些21 kDa的蛋白属于蛋白酪氨酸磷酸酶家族，含有典型的CX 5 R活性位点基序。对磷酸化底物的亲核攻击由Cys进行，而Arg和来自P-环中插入残基的几个骨架酰胺与磷酸部分配位。PRL与活性位点区域外的其他PTPases几乎没有序列相似性，
PRL enzymes have become highly sought after targets for drug design because of their involvement in metastatic cancer. Elevated levels of PRL-1 and PRL-3 have been shown to trigger metastasis, and PRL-1 and PRL-2 promote cellular transformation and tumorigenesis (Zeng et al., 2003; Saha et al., 2001; Cates et al., 1996). PRL-1 was originally identified as an early response gene involved in liver regeneration following partial hepatectomy in rats (Diamond et al., 1994). PRL enzymes are found only in multicellular eukaryotic organisms. Three isoforms exist in mammals, and C. elegans and Drosophila each appear to have a single homolog. A distinguishing feature of the PRLs is their C-terminal CaaX motif, which directs farnesylation of the Cys (Zeng et al., 2000). The modified protein can be altered further by proteolysis of the two aliphatic residues (aa) and additional C-terminal residue (X), and by α-carboxyl methylation of the new C-terminal farnesyl-Cys (Clarke, 1992). In addition, the PRL phosphatases encode a highly basic region near the C-terminus, which may act as a nuclear localization signal or secondary membrane binding motif.These 21 kDa proteins belong to the protein tyrosine phosphatase (PTPase) family and contain the canonical CX5R active-site motif. Nucleophilic attack on phosphorylated substrates is carried out by the Cys, while the Arg and several backbone amides from intervening residues in the P-loop coordinate the phosphate moiety. PRLs have little sequence similarity to other PTPases outside of the active site region and appear