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首页> 外文期刊>The Journal of Immunology: Official Journal of the American Association of Immunologists >TNF receptor family member BCMA (B cell maturation) associates with TNF receptor-associated factor (TRAF) 1, TRAF2, and TRAF3 and activates NF-kappa B, elk-1, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase.
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TNF receptor family member BCMA (B cell maturation) associates with TNF receptor-associated factor (TRAF) 1, TRAF2, and TRAF3 and activates NF-kappa B, elk-1, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase.

机译:TNF受体家族成员BCMA(B细胞成熟)与TNF受体相关因子(TRAF)1,TRAF2和TRAF3相关联,并激活NF-κB,elk-1,c-Jun N端激酶和p38促分裂原激活蛋白激酶。

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摘要

BCMA (B cell maturation) is a nonglycosylated integral membrane type I protein that is preferentially expressed in mature B lymphocytes. Previously, we reported in a human malignant myeloma cell line that BCMA is not primarily present on the cell surface but lies in a perinuclear structure that partially overlaps the Golgi apparatus. We now show that in transiently or stably transfected cells, BCMA is located on the cell surface, as well as in a perinulear Golgi-like structure. We also show that overexpression of BCMA in 293 cells activates NF-kappa B, Elk-1, the c-Jun N-terminal kinase, and the p38 mitogen-activated protein kinase. Coimmunoprecipitation experiments performed in transfected cells showed that BCMA associates with TNFR-associated factor (TRAF) 1, TRAF2, and TRAF3 adaptor proteins. Analysis of deletion mutants of the intracytoplasmic tail of BCMA showed that the 25-aa protein segment, from position 119 to 143, conserved between mouse and human BCMA, is essential for its association with the TRAFs and the activation of NF-kappa B, Elk-1, and c-Jun N-terminal kinase. BCMA belongs structurally to the TNFR family. Its unique TNFR motif corresponds to a variant motif present in the fourth repeat of the TNFRI molecule. This study confirms that BCMA is a functional member of the TNFR superfamily. Furthermore, as BCMA is lacking a "death domain" and its overexpression activates NF-kappa B and c-Jun N-terminal kinase, we can reasonably hypothesize that upon binding of its corresponding ligand BCMA transduces signals for cell survival and proliferation.
机译:BCMA(B细胞成熟)是一种非糖基化的I型完整膜蛋白,在成熟B淋巴细胞中优先表达。以前,我们在人类恶性骨髓瘤细胞系中报道,BCMA并非主要存在于细胞表面,而是位于部分与高尔基体重叠的核周结构中。现在我们表明,在瞬时或稳定转染的细胞中,BCMA位于细胞表面以及沿核的高尔基样结构中。我们还显示,在293细胞中BCMA的过度表达会激活NF-κB,Elk-1,c-Jun N末端激酶和p38促丝裂原激活的蛋白激酶。在转染的细胞中进行的共免疫沉淀实验表明,BCMA与TNFR相关因子(TRAF)1,TRAF2和TRAF3衔接蛋白缔合。 BCMA胞质尾巴缺失突变体的分析表明,从119位到143位的25-aa蛋白区段在小鼠和人BCMA之间保守,对于与TRAFs结合以及NF-κB,麋鹿的激活至关重要。 -1和c-Jun N末端激酶。 BCMA在结构上属于TNFR家族。其独特的TNFR基序对应于TNFRI分子第四重复序列中的变异基序。这项研究证实BCMA是TNFR超家族的功能性成员。此外,由于BCMA缺少“死亡结构域”,并且其过度表达激活了NF-κB和c-Jun N末端激酶,因此我们可以合理地假设,结合其相应的配体后,BCMA会转导细胞存活和增殖的信号。

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