Paired immunoglobulin-like receptor B (PIR-B) inhibits BCR-induced activation of Syk and Btk by SHP-1
Paired immunoglobulin-like receptor B (PIR-B) inhibits BCR-induced activation of Syk and Btk by SHP-1
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DOI：
10.1038/sj.onc.1202552
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发表时间：
1999-04-08
期刊：
影响因子：
8
通讯作者：
Kurosaki, T
中科院分区：
文献类型：
--
作者：
Maeda, A;Scharenberg, AM;Kurosaki, T
配对免疫球蛋白样受体B （PIR-B）与B细胞抗原受体（BCR）的结合可阻断抗原诱导的B细胞活化。这种抑制部分是通过将SHP-1和SHP-2募集到PIR-B细胞质域中磷酸化的ITIMs介导的；然而，这些磷酸酶的分子靶点仍然是难以捉摸的。在这里，我们发现PIR-B连接抑制bcr诱导的Ig α /Ig β、Syk、Btk和磷脂酶C (PLC)- γ 2的酪氨酸磷酸化。过表达一种催化失活的SHP-1可阻止PIR-B介导的Syk、Btk和PLC- γ 2酪氨酸磷酸化的抑制。SHP-1介导的Syk和Btk去磷酸化导致其激酶活性降低，进而抑制PLC-gamma 2的酪氨酸磷酸化。此外，我们定义了Lan介导PIR-B酪氨酸磷酸化的必要条件。基于这些结果，我们提出了PIR-B介导的抑制信号传导模型，其中PIR-B和BCR的结合导致Lyn磷酸化ITIMs，随后募集SHP-1，并通过Syk和Btk的去磷酸化抑制BCR诱导的肌醇1,4,5-三磷酸的产生。
Coligation of paired immunoglobulin-like receptor B (PIR-B) with B cell antigen receptor (BCR) blocks antigen-induced B cell activation. This inhibition is mediated in part by recruitment of SHP-1 and SHP-2 to the phosphorylated ITIMs in the cytoplasmic domain of PIR-B; however the molecular target(s) of these phosphatases remain elusive. Here,ve show that PIR-B ligation inhibits the BCR-induced tyrosine phosphorylation of Ig alpha/Ig beta, Syk, Btk and phospholipase C (PLC)-gamma 2 Overexpression of a catalgtically inactive form of SHP-1 prevents the PIR-B-mediated inhibition: of tyrosine phosphorylation of Syk, Btk, and PLC-gamma 2. Dephosphorylation of Syk and Btk mediated by SHP-1 leads to a decrease of their kinase activity, which in turn inhibits tyrosine phosphorylation of PLC-gamma 2. Furthermore, we define a requirement for Lan in mediating tyrosine phosphorylation of PIR-B, Based on these results, we propose a model of PIR-B-mediated inhibitory signaling in which coligation of PIR-B and BCR results in phosphorylation of ITIMs by Lyn, subsequent recruitment of SHP-1, and a resulting inhibition of the BCR-induced inositol 1,4,5-trisphosphate generation by dephosphorylation of Syk and Btk.