Cell surface receptors Ly-9 and CD84 recruit the X-linked lymphoproliferative disease gene product SAP.
Cell surface receptors Ly-9 and CD84 recruit the X-linked lymphoproliferative disease gene product SAP.
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DOI：
10.1182/blood.v97.12.3867
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发表时间：
2001-06
期刊：
影响因子：
20.3
通讯作者：
J. Sayós;M. Martín;A. Chen;M. Simarro;D. Howie;M. Morra;P. Engel;C. Terhorst
中科院分区：
文献类型：
--
作者：
J. Sayós;M. Martín;A. Chen;M. Simarro;D. Howie;M. Morra;P. Engel;C. Terhorst
X连锁淋巴组织增生性疾病（XLP）是一种罕见的免疫性疾病，通常由 Epstein-Barr 病毒感染引发。主要疾病表现包括致命性急性传染性单核细胞增多症、B细胞淋巴瘤和进行性丙种球蛋白异常血症。 SAP/SH2D1A 是 XLP 基因突变的产物，是一种小蛋白质，包含单个 SH2 结构域和 26 个氨基酸的短尾。 SAP 与细胞表面受体 SLAM 和 2B4 细胞质尾部的特定基序结合，阻止磷酸酶 SHP-2 的募集。据报道，造血细胞上差异表达的两种相关糖蛋白Ly-9和CD84也招募SAP。 SAP 和 Ly-9 或 CD84 之间的相互作用通过 COS 细胞转染和淋巴细胞中的新型酵母 2 杂交系统进行了分析。当 Ly-9 或 CD84 细胞质尾部的特定酪氨酸残基被磷酸化时，SAP 的募集是最有效的。结论是，在活化的 T 细胞中，SAP 蛋白结合并调节通过 SLAM、2B4、CD84 和 Ly-9 的参与启动的信号转导事件。这表明这 4 种细胞表面受体引发的功能失调信号通路的组合可能导致 XLP 的复杂表型。 （血。2001；97：3867-3874）
X-linked lymphoproliferative disease (XLP) is a rare immune disorder commonly triggered by infection with Epstein-Barr virus. Major disease manifestations include fatal acute infectious mononucleosis, B-cell lymphoma, and progressive dys-gammaglobulinemia. SAP/SH2D1A, the product of the gene mutated in XLP, is a small protein that comprises a single SH2 domain and a short tail of 26 amino acids. SAP binds to a specific motif in the cytoplasmic tails of the cell surface receptors SLAM and 2B4, where it blocks recruitment of the phosphatase SHP-2. Here it is reported that Ly-9 and CD84, 2 related glycoproteins differentially expressed on hematopoietic cells, also recruit SAP. Interactions between SAP and Ly-9 or CD84 were analyzed using a novel yeast 2-hybrid system, by COS cell transfections and in lymphoid cells. Recruitment of SAP is most efficient when the specific tyrosine residues in the cytoplasmic tails of Ly-9 or CD84 are phosphorylated. It is concluded that in activated T cells, the SAP protein binds to and regulates signal transduction events initiated through the engagement of SLAM, 2B4, CD84, and Ly-9. This suggests that combinations of dysfunctional signaling pathways initiated by these 4 cell surface receptors may cause the complex phenotypes of XLP. (Blood. 2001;97:3867-3874)