INVOLVEMENT OF CRAF1, A RELATIVE OF TRAF, IN CD40 SIGNALING

INVOLVEMENT OF CRAF1, A RELATIVE OF TRAF, IN CD40 SIGNALING
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DOI:
10.1126/science.7533327
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发表时间:
1995-03-10
期刊:
影响因子:
56.9
通讯作者:
BALTIMORE, D
BALTIMORE, D
中科院分区:
综合性期刊1区
文献类型:
--
作者:
CHENG, GH;CLEARY, AM;BALTIMORE, D

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CD 40是B淋巴细胞表面上的受体,其活化导致B细胞存活、生长和分化。酵母双杂交筛选鉴定了一种基因CRAF 1,其编码通过与肿瘤坏死因子-α(TNF-α)受体相关因子相似的区域直接与CD 40胞质尾相互作用的蛋白质。截短的CRAF 1基因的过表达抑制了CD 40介导的CD 23上调。CRAF 1的一个区域与TNF-α受体相关因子TRAF 1和TRAF 2相似,因此定义了一个共享的TRAF-C结构域,该结构域对于CD 40结合和同源二聚化是必要和充分的。CRAF 1序列还预测了一个长的两亲性螺旋,五个锌指的模式和一个锌环指。TNF受体超家族的其他成员可能在其信号转导过程中使用CRAF相关蛋白。
CD40 is a receptor on the surface of B lymphocytes, the activation of which leads to B cell survival, growth, and differentiation. A yeast two-hybrid screen identified a gene, CRAF1, encoding a protein that interacts directly with the CD40 cytoplasmic tail through a region of similarity to the tumor necrosis factor-alpha (TNF-alpha) receptor-associated factors. Overexpression of a truncated CRAF1 gene inhibited CD40-mediated up-regulation of CD23. A region of CRAF1 was similar to the TNF-alpha receptor-associated factors TRAF1 and TRAF2 and so defined a shared TRAF-C domain that was necessary and sufficient for CD40 binding and homodimerization. The CRAF1 sequence also predicted a long amphipathic helix, a pattern of five zinc fingers, and a zinc ring finger. It is likely that other members of the TNF receptor superfamily use CRAF-related proteins in their signal transduction processes.