Differential phosphorylation of functional tyrosines in CD19 modulates B-lymphocyte activation
Differential phosphorylation of functional tyrosines in CD19 modulates B-lymphocyte activation
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CD19 中功能性酪氨酸的差异磷酸化调节 B 淋巴细胞活化
DOI：
10.1002/eji.200939848
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发表时间：
2010
期刊：
影响因子：
5.4
通讯作者：
Fujimoto M
中科院分区：
文献类型：
--
作者：
Ishiura N;Nakashima H;Watanabe R;Kuwano Y;Adachi T;Takahashi Y;Tsubata T;Okochi H;Tamaki K;Tedder TF;Fujimoto M
CD 19是一种B-细胞跨膜分子，对B-细胞活化至关重要。CD 19作为关键信号转导分子（包括林恩、PI 3 K和Vav）的支架蛋白，通过CD 19-Y513、CD 19-Y 482和CD 19-Y391的磷酸化为这些分子提供对接位点。我们研究了在B-细胞活化过程中，使用对这些磷酸化酪氨酸中的每一种具有特异性的Ab的CD 19酪氨酸磷酸化的过程。BCR结合诱导差异酪氨酸磷酸化，因为CD 19-Y513磷酸化首先发生，而CD 19-Y 482磷酸化是延迟和短暂的。不同的BCR同种型表现出不同的CD 19磷酸化模式：IgG-BCR连接导致CD 19-Y513的磷酸化更快，CD 19-Y391的磷酸化更强烈。这影响了涉及Vav、PI 3 K和Akt的CD 19介导的下游通路。此外，CD 19的磷酸化谱根据其质膜位置而明显不同。Y513磷酸化的CD 19几乎全部位于脂筏内，而Y 482和Y391磷酸化的CD 19在脂筏内外均存在。此外，所有三个酪氨酸的磷酸化显着增强和延长后，BCR和CD 40的同时刺激。因此，磷酸化模式的变化可能有助于CD 19调节信号转导的复杂性。
CD19 is a B‐cell transmembrane molecule that is critical for B‐cell activation. CD19 serves as a scaffold protein for key signal transduction molecules including Lyn, PI3K, and Vav, by providing docking sites for these moleculesviaphosphorylation of CD19‐Y513, CD19‐Y482, and CD19‐Y391. We investigated the process of CD19 tyrosine phophorylation during B‐cell activation using Ab specific for each of these phosphorylated tyrosines. BCR engagement induced differential tyrosine phosphorylation, as CD19‐Y513phophorylation occurred first, and CD19‐Y482phosphorylation was delayed and transient. Different BCR isotypes exhibited distinct patterns of CD19 phosphorylation: IgG‐BCR ligation resulted in faster phosphorylation of CD19‐Y513and more intense phosphorylation of CD19‐Y391than IgM‐BCR ligation. This affected CD19‐mediated downstream pathways involving Vav, PI3K, and Akt. Additionally, the phosphorylation profile of CD19 differed distinctly according to its plasma membrane location. CD19 phosphorylated at Y513was almost exclusively located within lipid rafts, whereas phosphorylated Y482and Y391were found both inside and outside of the rafts. Furthermore, the phosphorylation of all three tyrosines was remarkably enhanced and prolonged following the simultaneous stimulation of BCR and CD40. Thus, variations in phosphorylation patterns may contribute to the complexity of CD19‐regulated signal transduction.