B cell antigen receptor and CD40 differentially regulate CD22 tyrosine phosphorylation
B cell antigen receptor and CD40 differentially regulate CD22 tyrosine phosphorylation
复制标题
DOI：
10.4049/jimmunol.176.2.873
复制
发表时间：
2006-01-15
影响因子：
4.4
通讯作者：
Sato, S
中科院分区：
文献类型：
--
作者：
Fujimoto, M;Kuwano, Y;Sato, S
淋巴细胞上的细胞表面分子正向或负向调节Ag受体信号传导，从而调节细胞的命运。CD22是B细胞特异性的细胞表面蛋白，其在胞质尾区中含有多个ITIM，并且关键地调节B细胞活化和存活。CD22对B细胞信号传导的调节是复杂的，因为CD22在各种情况下可以具有积极和消极的作用。我们产生了磷酸化特异性多克隆抗体反应四个主要的CD22酪氨酸基序（Y762，Y807，Y822和Y842），并分析了这些酪氨酸残基的磷酸化的模式和强度。酪氨酸基序Y762、Y822和Y842被认为是ITIM，而另一个Y807被认为对Grb2募集很重要。约10%的四个酪氨酸残基组成性磷酸化。在抗IgM连接后，CD22 Y762经历了最快速的磷酸化，而所有四个酪氨酸残基最终以类似于细胞中所有CD22分子的35%被同等地磷酸化。相比之下，抗CD40刺激特异性上调两个ITIM基序Y762和Y842内的抗IgM诱导的酪氨酸磷酸化，这与体内发现的CD22在CD40信号传导中的负作用一致。因此，CD22磷酸化不仅在数量上而且在质量上受到不同刺激的调节，这可能决定B细胞信号传导的结果。
Cell surface molecules on lymphocytes positively or negatively modulate the Ag receptor signaling, and thus regulate the fate of the cell. CD22 is a B cell-specific cell surface protein that contains multiple ITIMs in the cytoplasmic tail, and critically regulates B cell activation and survival. CD22 regulation on B cell signaling is complex because CD22 can have both positive and negative roles in various contexts. We generated phosphospecific polyclonal Abs reacting four major CD22 tyrosine motifs (Y762, Y807, Y822, and Y842) and analyzed the pattern and intensity of phosphorylation of these tyrosine residues. The tyrosine motifs, Y762, Y822, and Y842, are considered as ITIM, whereas the other, Y807, is suggested to be important for Grb2 recruitment. Approximately 10% of the four tyrosine residues were constitutively phosphorylated. Upon anti-IgM ligation, CD22 Y762 underwent most rapid phosphorylation, whereas all four tyrosine residues were eventually phosphorylated equally at similar to 35% of all CD22 molecules in the cell. By contrast, anti-CD40 stimulation specifically up-regulated anti-IgM-induced phosphorylation of tyrosines within two ITIM motifs, Y762 and Y842, which was consistent with in vivo finding of the negative role of CD22 in CD40 signaling. Thus, CD22 phosphorylation is not only quantitatively but also qualitatively regulated by different stimulations, which may determine the outcome of B cell signaling.