NFAM1, an immunoreceptor tyrosine-based activation motif-bearing molecule that regulates B cell development and signaling
NFAM1, an immunoreceptor tyrosine-based activation motif-bearing molecule that regulates B cell development and signaling
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DOI：
10.1073/pnas.0401119101
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发表时间：
2004-05-25
影响因子：
11.1
通讯作者：
Saito, T
中科院分区：
文献类型：
--
作者：
Ohtsuka, M;Arase, H;Saito, T
通过使用编码CD 8嵌合蛋白的逆转录病毒文库和活化T细胞核因子（NFAT）-GFP报告细胞系开发功能性cDNA克隆系统以鉴定诱导NFAT活化的分子。通过使用这种策略，NFAT活化分子1（NFAM 1）被克隆为免疫受体酪氨酸基活化基序（ITAM）承载的细胞表面分子，其属于IG超家族，并且主要在脾B和T细胞中表达。NFAM 1交联诱导ITAM磷酸化、ZAP-70/Syk募集、NFAT活化和细胞因子产生。在骨髓嵌合体和转基因小鼠中NFAM 1的体内过表达以ITAM依赖的方式诱导早期B细胞发育的严重损害。在表达NFAM 1的B细胞中，B细胞抗原受体刺激诱导NFAM 1易位至脂筏，并且NFAM 1共交联增强了B细胞抗原受体信号传导。结果表明，NFAM 1通过其ITAM调节B细胞信号传导，ITAM调节B细胞发育。
A functional cDNA cloning system was developed by using a retrovirus library encoding CD8-chimeric proteins and a nuclear factor of activated T cells (NFAT)-GFP reporter cell line to identify molecules inducing NFAT activation. By using this strategy, NFAT activating molecule 1 (NFAM1) was cloned as an immunoreceptor tyrosine-based activation motif (ITAM)-bearing cell surface molecule belonging to the Ig superfamily and is predominantly expressed in spleen B and T cells. NFAM1 crosslinking induced ITAM phosphorylation, ZAP-70/Syk recruitment, NFAT activation, and cytokine production. In vivo overexpression of NFAM1 in bone marrow chimeras and transgenic mice induced severe impairment of early B cell development in an ITAM-dependent manner. in NFAM1-expressing B cells, B cell antigen receptor stimulation induced NFAM1 translocation to lipid raft, and NFAM1 co-crosslinking augmented B cell antigen receptor signaling. The results suggest that NFAM1 modulates B cell signaling through its ITAM, which regulates B cell development.