The role of the DAP12 signal in mouse myeloid differentiation

The role of the DAP12 signal in mouse myeloid differentiation
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DOI:
10.4049/jimmunol.165.7.3790
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发表时间:
2000-10-01
影响因子:
4.4
通讯作者:
Katagiri, M
Katagiri, M
中科院分区:
医学2区
文献类型:
--
作者:
Aoki, N;Kimura, S;Katagiri, M

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DAP12.DAP12是最近克隆的一种带有免疫受体酪氨酸激活基序的跨膜适配分子,与NK激活受体相关,以往的报道表明,DAP12信息不仅在NK细胞中检测到,而且在粒细胞、单核细胞、树突状细胞和巨噬细胞中也可检测到,本研究发现DAP12蛋白在巨噬细胞相关细胞系和器官中有显著水平的表达。此外,我们观察到DAP12的表达增加,在内毒素诱导的M1细胞向巨噬细胞分化后,为了检测DAP12在髓系细胞系中的作用,我们建立了M1 FLAG-DAP12转基因细胞(FDAP-M1),并证明了显著的形态学变化;通过DAP12信号转导引起的FDAP-M1细胞表面表型分析显示巨噬细胞标志物CD11b、2,4G2和黏附分子B7-2上调,此外,经DAP12刺激后,磷酸化的FLAG-DAP12可以被抗磷酸酪氨酸单抗免疫沉淀,这些发现共同表明直接的DAP12信号在巨噬细胞分化中有重要作用。
DAP12. is a recently cloned, immunoreceptor tyrosine-based activation motif-bearing transmembrane adapter molecule that is associated with the NK-activating receptors, Previous reports showed that the DAP12 message could be detected not only in NK cells but also in granulocytes, monocytes, dendritic cells, and macrophages, In this study we found a significant level of DAP12 protein expression in macrophage-related cell lines and organs. Additionally, we observed increased expression of DAP12, after LPS-induced differentiation of M1 cells into macrophages, To examine the role of DAP12 in the myeloid cell lineage, we established M1 FLAG-DAP12 transfectants (FDAP-M1) and demonstrated the marked;morphological changes in FDAP-M1 cells caused by signaling through DAP12 Cell surface phenotypic analysis showed up-regulation of macrophage markers CD11b, 2,4G2, and adhesion molecule B7-2, Additionally, after stimulation through DAP12, phosphorylated FLAG -DAP12 could be immunoprecipitated using anti-phosphotyrosine mAbs, Collectively, these findings indicate that direct DAP12 signaling has an important role in macrophage differentiation.