Homomultimeric complexes of CD22 in B cells revealed by protein-glycan cross-linking
Homomultimeric complexes of CD22 in B cells revealed by protein-glycan cross-linking
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DOI：
10.1038/nchembio713
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发表时间：
2005-07-01
影响因子：
14.8
通讯作者：
Paulson, JC
中科院分区：
文献类型：
--
作者：
Han, S;Collins, BE;Paulson, JC
CD22是B细胞受体信号的负调节因子，其胞浆结构域(1)通过磷酸化的免疫受体酪氨酸抑制基序(1)募集含有SH2结构域的磷酸酶1。与唾液酸结合的免疫球蛋白样凝集素或Siglec家族的其他成员一样，CD22的胞外N末端免疫球蛋白结构域与含有唾液酸的糖配体结合，唾液酸在B细胞糖蛋白上高度表达。B细胞糖蛋白结合CD22在顺式‘掩蔽’配体结合域(3)，调节其作为一个B细胞信号调节器的活性(4-6)。为了评估细胞-表面顺式配体的相互作用，我们开发了一种新的方法来原位光亲和交联CD22的葡聚糖配体。值得注意的是，CD45、表面免疫球蛋白(SIGM)和其他在体外与CD22结合的糖蛋白(7，8)似乎不是CD22原位的重要顺式配体。相反，CD22似乎识别邻近CD22分子的葡聚糖为顺式配体，形成同源多聚体复合体。
CD22 is a negative regulator of B-cell receptor signaling, an activity mediated by recruitment of SH2 domain-containing phosphatase 1 through a phosphorylated immunoreceptor tyrosine inhibitory motif in its cytoplasmic domain(1). As in other members of the sialic acid-binding immunoglobulin-like lectin, or siglec, family, the extracellular N-terminal immunoglobulin domain of CD22 binds to glycan ligands containing sialic acid, which are highly expressed on B-cell glycoproteins(2). B-cell glycoproteins bind to CD22 in cis and 'mask' the ligand-binding domain(3), modulating its activity as a regulator of B-cell signaling(4-6). To assess cell-surface cis ligand interactions, we developed a new method for in situ photoaffinity cross-linking of glycan ligands to CD22. Notably, CD45, surfaceIgM (sIgM) and other glycoproteins that bind to CD22 in vitro(7,8) do not appear to be important cis ligands of CD22 in situ. Instead, CD22 seems to recognize glycans of neighboring CD22 molecules as cis ligands, forming homomultimeric complexes.