Truncation of C-mip (Tc-mip), a new proximal signaling protein, induces c-maf Th2 transcription factor and cytoskeleton reorganization.

Truncation of C-mip (Tc-mip), a new proximal signaling protein, induces c-maf Th2 transcription factor and cytoskeleton reorganization.
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DOI:
10.1084/jem.20030566
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发表时间:
2003-09-01
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Sahali D
Sahali D
中科院分区:
其他
文献类型:
--
作者:
Grimbert P;Valanciute A;Audard V;Pawlak A;Le gouvelo S;Lang P;Niaudet P;Bensman A;Guellaën G;Sahali D

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几种观点认为微小病变型肾病综合征(MCNS)是由未知的全身性T细胞功能紊乱引起的。通过筛选T细胞复发的cDNA文库,我们发现了一个新的含有Pleckstrin Homology(PH)结构域的蛋白,该蛋白由位于染色体16q24上的一个基因编码。确定了两个可供选择的转录本。第一种(c-MIP)在胎肝、胎肾和外周血单个核细胞(PBMCs)中表达,但在MCNS患者的PBMCs中表达较弱。第二种形式(TC-MIP,代表截短的c-maf诱导蛋白),对应于消减的转录本,缺少NH2末端的PH结构域。TC-MIP的表达仅限于胎肝、胸腺和单核细胞集落刺激因子(MCNS)外周血单个核细胞(PBMCs),而其特异性募集于CD4+T细胞亚群。在T细胞Jurkat中过表达TC-MIP可诱导c-MAF,反式激活IL-4基因,下调干扰素γ的表达,这是Th2型承诺的特征。此外,TC-MIP的过表达通过PI3激酶非依赖的途径诱导了Src的磷酸化、T细胞的聚集和细胞骨架相关的L-纤溶酶的细胞重新分布。因此,TC-MIP代表了第一个被识别的蛋白质,它将近端信号与c-maf诱导联系起来。
Several arguments suggest that minimal change nephrotic syndrome (MCNS) results from yet unknown systemic disorder of T cell function. By screening a cDNA library from T cell relapse, we identified a new pleckstrin homology (PH) domain-containing protein encoded by a gene located on chromosome 16q24. Two alternative transcripts were identified. The first species (c-mip) was expressed in fetal liver, kidney, and peripheral blood mononuclear cells (PBMCs), but weakly detected in PBMCs from MCNS patients. The second form (Tc-mip, standing for truncated c-maf inducing protein), corresponds to subtracted transcript and lacks the NH2-terminal PH domain. The expression of Tc-mip was restricted to fetal liver, thymus, and MCNS PBMCs where it was specifically recruited in CD4+ T cells subset. Overexpression of Tc-mip in T cell Jurkat induced c-maf, transactivated the interleukin 4 gene and down-regulated the interferon γ expression, characteristic of a Th2 commitment. Moreover, the overexpression of Tc-mip induced Src phosphorylation, T cell clustering, and a cellular redistribution of the cytoskeleton-associated L-plastin, by a PI3 kinase independent pathway. Tc-mip represents therefore the first identified protein, which links proximal signaling to c-maf induction.
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