Cloning and characterization of human Siglec-11 - A recently evolved signaling molecule that can interact with SHP-1 and SHP-2 and is expressed by tissue macrophages, including brain microglia
Cloning and characterization of human Siglec-11 - A recently evolved signaling molecule that can interact with SHP-1 and SHP-2 and is expressed by tissue macrophages, including brain microglia
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DOI：
10.1074/jbc.m202833200
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发表时间：
2002-07-05
影响因子：
4.8
通讯作者：
Varki, A
中科院分区：
文献类型：
--
作者：
Angata, T;Kerr, SC;Varki, A
Siglecs是免疫球蛋白超家族的唾液酸识别动物凝集素。我们已经克隆并表征了一种新的人类分子Siglec-11，其属于CD 33/Siglec-3相关Siglees亚组。与该亚组中的其他结构域一样，Siglec-11的胞质结构域在细胞的过钒酸盐处理后在酪氨酸残基处磷酸化，然后募集蛋白酪氨酸磷酸酶SHP-1和SHP-2。然而，Siglec-11相对于其他CD 33/Siglec-3相关Siglec具有几个新特征。首先，它特异性结合α 2 -8-连接的唾液酸。其次，与其他CD 33/Siglec-3相关Siglec不同，Siglec-11未在外周血白细胞中发现。相反，我们观察到它在各种组织中的巨噬细胞上的表达，如肝枯否细胞。第三，它也在脑小胶质细胞上表达，从而成为第二个在神经系统中发现的Siglec。第四，虽然Siglec-11基因位于人类19号染色体上，但它位于该染色体上先前描述的CD 33/Siglec-3相关Siglec簇之外。第五，对基因组数据库的分析表明，Siglec-11没有小鼠直系同源物，它可能是最后一个被报道的典型人类Siglec。最后，尽管Siglec-11在其细胞外结构域中显示出与人Siglec-10的显著序列相似性，但胞质尾似乎仅是远亲。Siglec-11基因周围的基因组区域的分析表明，它实际上是一种嵌合分子，由相对较新的基因复制和重组事件产生，涉及密切相关的祖先Siglec基因的胞外结构域（随后成为假基因）和来自另一个祖先Siglec的跨膜和胞质尾。
Siglecs are sialic acid-recognizing animal lectins of the immunoglobulin superfamily. We have cloned and characterized a novel human molecule, Siglec-11, that belongs to the subgroup of CD33/Siglec-3-related Siglees. As with others in this subgroup, the cytosolic domain of Siglec-11 is phosphorylated at tyrosine residue(s) upon pervanadate treatment of cells and then recruits the protein-tyrosine phosphatases SHP-1 and SHP-2. However, Siglec-11 has several novel features relative to the other CD33/Siglec-3-related Siglecs. First, it binds specifically to alpha2-8-linked sialic acids. Second, unlike other CD33/Siglec-3-related Siglecs, Siglec-11 was not found on peripheral blood leukocytes. Instead, we observed its expression on macrophages in various tissues, such as liver Kupffer cells. Third, it was also expressed on brain microglia, thus becoming the second Siglec to be found in the nervous system. Fourth, whereas the Siglec-11 gene is on human chromosome 19, it lies outside the previously described CD33/Siglec-3-related Siglec cluster on this chromosome. Fifth, analyses of genome data bases indicate that Siglec-11 has no mouse ortholog and that it is likely to be the last canonical human Siglec to be reported. Finally, although Siglec-11 shows marked sequence similarity to human Siglec-10 in its extracellular domain, the cytosolic tail appears only distantly related. Analysis of genomic regions surrounding the Siglec-11 gene suggests that it is actually a chimeric molecule that arose from relatively recent gene duplication and recombination events, involving the extracellular domain of a closely related ancestral Siglec gene (which subsequently became a pseudogene) and a transmembrane and cytosolic tail derived from another ancestral Siglec.