Large-scale proteomic analysis of tyrosine-phosphorylation induced by T-cell receptor or B-cell receptor activation reveals new signaling pathways
Large-scale proteomic analysis of tyrosine-phosphorylation induced by T-cell receptor or B-cell receptor activation reveals new signaling pathways
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DOI：
10.1002/pmic.200900011
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发表时间：
2009-07-01
期刊：
影响因子：
3.4
通讯作者：
Nakayama, Keiichi I.
中科院分区：
文献类型：
--
作者：
Matsumoto, Masaki;Oyamada, Koji;Nakayama, Keiichi I.
T细胞受体（TCR）和B细胞受体（BCR）的激活可促进属于相似功能类别的蛋白质的酪氨酸磷酸化，但导致不同的细胞反应。尚未描述提供TCR或BCR下游信号传导途径概述的大规模分析，因此尚不清楚这些途径的哪些组分是共享的，哪些是特异性的。我们现在已经进行了系统的分析，并提供了一个全面的清单酪氨酸磷酸化蛋白质（PY蛋白质组）的定量数据，其丰度在T细胞，B细胞，和nonlymphoid细胞系。我们的研究结果导致识别新的酪氨酸磷酸化的蛋白质和信号通路，以前没有牵连的免疫受体信号转导，如网格蛋白，闭锁小带2，真核生物翻译起始因子3和RhoH，表明TCR或BCR信号可能与下游过程，如内吞作用，细胞粘附和翻译。因此，酪氨酸磷酸化的比较和定量研究有可能扩大信号网络的知识，并促进在系统水平上的信号转导的理解。
Activation of the T-cell receptor (TCR) and that of the B-cell receptor (BCR) elicits tyrosine-phosphorylation of proteins that belongs to similar functional categories, but result in distinct cellular responses. Large-scale analyses providing an overview of the signaling pathways downstream of TCR or BCR have not been described, so it has been unclear what components of these pathways are shared and which are specific. We have now performed a systematic analysis and provide a comprehensive list of tyrosine-phosphorylated proteins (PY proteome) with quantitative data on their abundance in T cell, B cell, and nonlymphoid cell lines. Our results led to the identification of novel tyrosine-phosphorylated proteins and signaling pathways not previously implicated in immunoreceptor signal transduction, such as clathrin, zonula occludens 2, eukaryotic translation initiation factor 3, and RhoH, suggesting that TCR or BCR signaling may be linked to downstream processes such as endocytosis, cell adhesion, and translation. Thus comparative and quantitative studies of tyrosine-phosphorylation have the potential to expand knowledge of signaling networks and to promote understanding of signal transduction at the system level.