Nitration of PECAM-1 ITIM tyrosines abrogates phosphorylation and SHP-2 binding
Nitration of PECAM-1 ITIM tyrosines abrogates phosphorylation and SHP-2 binding
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DOI：
10.1016/s0006-291x(02)02060-0
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发表时间：
2002-09-06
影响因子：
3.1
通讯作者：
Newman, PJ
中科院分区：
文献类型：
--
作者：
Newman, DK;Hoffman, S;Newman, PJ
血小板内皮细胞粘附分子-1 (PECAM-1) 是一种细胞粘附分子，具有基于细胞质免疫感受器酪氨酸的抑制基序 (ITIM)，当磷酸化时，可结合含有 Src 同源 2 结构域的蛋白酪氨酸磷酸酶 (SHP-2)。 PECAM-1 在内皮细胞连接处表达，暴露于炎症中间体可能会导致翻译后氨基酸修饰，从而影响蛋白质结构和功能。在患病组织中发现了在炎症部位产生的活性氮（RNS）、硝酸盐酪氨酸残基以及通过酪氨酸硝化修饰的几种蛋白质。我们在此表明，RNS（过氧亚硝酸盐）诱导全长细胞 PECAM-1 和纯化的重组 PECAM-1 细胞质结构域的硝化。胰蛋白酶片段的质谱分析揭示了 ITIM 酪氨酸 686 的定量硝化。在位置 686 含有 3-硝基酪氨酸的合成肽不能被磷酸化，也不能结合 SHP-2。这些数据表明 ITIM 酪氨酸硝化可能代表调节磷酸酪氨酸依赖性信号转导途径的机制。 (C) 2002 年爱思唯尔科学（美国）。版权所有。
Platelet-endothelial cell adhesion molecule-1 (PECAM-1) is a cell adhesion molecule with a cytoplasmic immumoreceptor tyrosine-based inhibitory motif (ITIM) that, when phosphorylated, binds Src homology 2 domain-containing protein-tyrosine phosphatase (SHP-2). PECAM-1 is expressed at endothelial cell junctions where exposure to inflammatory intermediates may result in post-translational amino acid modifications that affect protein structure and function. Reactive nitrogen species (RNS), which are produced at sites of inflammation, nitrate tyrosine residues, and several proteins modified by tyrosine nitration have been found in diseased tissue. We show here that the RNS, peroxynitrite, induced nitration of both full-length cellular PECAM-1 and a purified recombinant PECAM-1 cytoplasmic domain. Mass spectrometric analysis of tryptic fragments revealed quantitative nitration of ITIM tyrosine 686. A synthetic peptide containing 3-nitrotyrosine at position 686 could not be phosphorylated nor bind SHP-2. These data suggest that ITIM tyrosine nitration may represent a mechanism for modulating phosphotyrosine-dependent signal transduction pathways. (C) 2002 Elsevier Science (USA). All rights reserved.