A high-frequency polymorphism in exon 6 of the CD45 tyrosine phosphatase gene (PTPRC) resulting in altered isoform expression
A high-frequency polymorphism in exon 6 of the CD45 tyrosine phosphatase gene (PTPRC) resulting in altered isoform expression
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CD45 酪氨酸磷酸酶基因 (PTPRC) 外显子 6 的高频多态性导致亚型表达改变
DOI：
10.1073/pnas.0931490100
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发表时间：
2003
影响因子：
11.1
通讯作者：
E. Tchilian
中科院分区：
文献类型：
--
作者：
Tara Stanton;S. Boxall;K. Hirai;R. Dawes;S. Tonks;T. Yasui;Y. Kanaoka;N. Yuldasheva;O. Ishiko;W. Bodmer;P. Beverley;E. Tchilian
CD 45（白细胞共同）抗原是造血细胞特异性酪氨酸磷酸酶，对淋巴细胞中抗原受体介导的信号传导至关重要。该分子在细胞外结构域中经历复杂的选择性剪接，并且CD 45剪接的不同模式与不同的功能相关。缺乏CD 45会导致严重的联合免疫缺陷，由于外显子4的多态性，CD 45剪接的改变与免疫功能的改变有关。在这里，我们描述了一个多态性外显子6（A138 G）的基因编码的CD 45干扰选择性剪接。该多态性导致外显子6中Thr-47氨基酸替换为Ala，这是一个潜在的O-和N-连接的糖基化位点。这种外显子6 A138 G变异在日本人群中的频率为23.7%，但在高加索人群中不存在。来自携带A138 G变体的个体的外周血T细胞显示出表达A、B和C CD 45同种型的细胞比例的显著降低和高频率的CD 45 R 0+细胞。A138 G携带者的这些表型改变可能导致配体结合的变化、CD 45的同源二聚化和免疫反应的改变，这表明自然选择参与了A138 G携带者频率的控制。
CD45 (leukocyte common) antigen is a hemopoietic cell-specific tyrosine phosphatase essential for antigen receptor-mediated signaling in lymphocytes. The molecule undergoes complex alternative splicing in the extracellular domain, and different patterns of CD45 splicing are associated with distinct functions. Lack of CD45 leads to severe combined immunodeficiency, and alterations of CD45 splicing, because of a polymorphism in exon 4, have been associated with altered immune function. Here we describe a polymorphism in exon 6 (A138G) of the gene encoding CD45 that interferes with alternative splicing. The polymorphism results in an amino acid substitution of Thr-47 to Ala in exon 6, a potential O- and N-linked glycosylation site. This exon 6 A138G variant is present at a frequency of 23.7% in the Japanese population but is absent in Caucasoids. Peripheral blood T cells from individuals carrying the A138G variant show a significant decrease in the proportion of cells expressing the A, B, and C CD45 isoforms and a high frequency of CD45R0+ cells. These phenotypic alterations in the A138G carriers may lead to changes in ligand binding, homodimerization of CD45, and altered immune responses, suggesting the involvement of natural selection in controlling the A138G carrier frequency.