Identification and characterization of two related murine genes, Eat2a and Eat2b, encoding single SH2-domain adapters
Identification and characterization of two related murine genes, Eat2a and Eat2b, encoding single SH2-domain adapters
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DOI：
10.1007/s00251-005-0056-3
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发表时间：
2006-02-01
期刊：
影响因子：
3.2
通讯作者：
Lanyi, A
中科院分区：
文献类型：
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作者：
Calpe, S;Erdös, E;Lanyi, A
人ate -2 （SH2D1B）和SLAM-associated protein (SAP) （SH2D1A）是单个sh2结构域适配器，它们结合到6个信号化淋巴细胞激活分子（SLAM） （SLAMF1）相关受体的细胞质尾特异性酪氨酸残基上。在这里，我们报告说，与人类不同，小鼠和大鼠的Eat2基因是用相同的基因组组织复制的。小鼠Eat2a和Eat2b基因的编码区在核苷酸水平上具有91%的同源性，在蛋白水平上具有84%的同源性；同样，内含子的片段也是高度保守的。小鼠Eat2a mRNA在多种组织中表达，而Eat2b仅在小鼠自然杀伤细胞、CD8（+）停止T细胞和卵巢中检测到，表明后者的组织表达非常有限。在转染细胞中，EAT-2A和EAT-2B均与小鼠SLAM共免疫沉淀，并增强了SLAM细胞质尾部酪氨酸磷酸化。通过酵母双杂交实验确定，EAT-2A和EAT-2B都能与src样激酶Fyn、Hck、Lyn、Lck和Fgr结合。然而，与SAP不同，EAT-2蛋白与它们的激酶结构域结合，而不是与这些激酶的SH3结构域结合。综上所述，这些数据表明EAT-2A和EAT-2B都是将Src激酶招募到SLAM家族受体的适配器，其机制与SAP不同。
Human EAT-2 (SH2D1B) and SLAM-associated protein (SAP) (SH2D1A) are single SH2-domain adapters, which bind to specific tyrosine residues in the cytoplasmic tail of six signaling lymphocytic activation molecule (SLAM) (SLAMF1)-related receptors. Here we report that, unlike in humans, the mouse and rat Eat2 genes are duplicated with an identical genomic organization. The coding regions of the mouse Eat2a and Eat2b genes share 91% identity at the nucleotide level and 84% at the protein level; similarly, segments of introns are highly conserved. Whereas expression of mouse Eat2a mRNA was detected in multiple tissues, Eat2b was only detectable in mouse natural killer cells, CD8(+) stop T cells, and ovaries, suggesting a very restricted tissue expression of the latter. Both the EAT-2A and EAT-2B coimmunoprecipitated with mouse SLAM in transfected cells and augmented tyrosine phosphorylation of the cytoplasmic tail of SLAM. Both EAT-2A and EAT-2B bind to the Src-like kinases Fyn, Hck, Lyn, Lck, and Fgr, as determined by a yeast two-hybrid assay. However, unlike SAP, the EAT-2 proteins bind to their kinase domains and not to the SH3 domain of these kinases. Taken together, the data suggest that both EAT-2A and EAT-2B are adapters that recruit Src kinases to SLAM family receptors using a mechanism that is distinct from that of SAP.