Constitutive tyrosine phosphorylation of the inhibitory paired Ig-like receptor PIR-B
Constitutive tyrosine phosphorylation of the inhibitory paired Ig-like receptor PIR-B
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DOI：
10.1073/pnas.96.26.15086
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发表时间：
1999-12-21
影响因子：
11.1
通讯作者：
Cooper, MD
中科院分区：
文献类型：
--
作者：
Ho, LH;Uehara, T;Cooper, MD
PIR-A 和 PIR-B 是小鼠 B 淋巴细胞、树突状细胞和骨髓系细胞上的激活和抑制性 lg 样受体。 PIR-B 的抑制功能是通过其细胞质免疫受体酪氨酸抑制基序介导的，而 PIR-A 与 Fc 受体共同伽玛链配对形成激活受体复合物。在这些研究中，我们观察到巨噬细胞酸性 B 淋巴细胞上 PIR-B 分子的组成型酪氨酸磷酸化，与细胞激活状态无关。脾细胞 PIR-B 分子与 SHP-1 蛋白酪氨酸磷酸酶和 Lyn 蛋白酪氨酸激酶组成型相关。在 Lyn 缺陷小鼠中，PIR-B 酪氨酸磷酸化大大降低。出乎意料的是，在大多数骨髓细胞和 B 细胞系中未观察到 PIR-B 的酪氨酸磷酸化，但可以通过 PIR 分子的连接来诱导。最后，在 MHC I 类缺陷小鼠中，PIR-B 的磷酸化状态显着降低，但在 TAP1 或 MHC II 类表达缺陷的小鼠中则没有。这些发现表明 PIR-B 的生理抑制作用受内源性 MHC I 类配体调节。
PIR-A and PIR-B are activating and inhibitory lg-like receptors on murine B lymphocytes, dendritic cells, and myeloid-lineage cells. The inhibitory function of PIR-B is mediated via its cytoplasmic immunoreceptor tyrosine-based inhibitory motifs, whereas PIR-A pairs with the Fc receptor common gamma chain to form an activating receptor complex. In these studies, we observed constitutive tyrosine phosphorylation of PIR-B molecules on macrophages acid B lymphocytes, irrespective of the cell activation status. Splenocyte PIR-B molecules were constitutively associated with the SHP-1 protein tyrosine phosphatase and Lyn protein tyrosine kinase. In Lyn-deficient mice, PIR-B tyrosine phosphorylation was greatly reduced. Unexpectedly, tyrosine phosphorylation of PIR-B was not observed in most myeloid and B cell lines but could be induced by ligation of the PIR molecules. Finally, the phosphorylation status of PIR-B was significantly reduced in MHC class I-deficient mice, although not in mice deficient in TAP1 or MHC class II expression. These findings suggest a physiological inhibitory role for PIR-B that is regulated by endogenous MHC class I-like ligands.