Grf40, A novel Grb2 family member, is involved in T cell signaling through interaction with SLP-76 and LAT.
Grf40, A novel Grb2 family member, is involved in T cell signaling through interaction with SLP-76 and LAT.
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DOI：
10.1084/jem.189.9.1383
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发表时间：
1999-05-03
期刊：
影响因子：
--
通讯作者：
Sugamura K
中科院分区：
文献类型：
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作者：
Asada H;Ishii N;Sasaki Y;Endo K;Kasai H;Tanaka N;Takeshita T;Tsuchiya S;Konno T;Sugamura K
我们分子克隆了一个新的Grb 2家族成员，命名为Grf 40，含有共同的SH 3-SH 2-SH 3基序。Grf 40的表达主要在造血细胞，特别是T细胞中。Grf 40通过其SH 3结构域与76 kD的含SH 2结构域的白细胞蛋白（SLP-76）结合比Grb 2更紧密。顺便提及，Grf 40可能通过其SH 2结构域与用于活化T细胞（LAT）的接头结合。Jurkat细胞中野生型Grf 40的过表达诱导了T细胞受体（TCR）刺激后SLP-76依赖性白细胞介素（IL）-2启动子和活化T细胞核因子（NF-AT）活化的显著增加，而COOH末端SH 3缺失的Grf 40突变体缺乏IL-2启动子活性的任何可识别的增加。此外，SH 2缺失的Grf 40突变体导致这些调节活性的显著抑制，其效果明显强于SH 2缺失的Grb 2突变体。我们的数据表明，Grf 40是一种衔接分子，通过比Grb 2与SLP-76和LAT更有效的相互作用参与TCR介导的信号传导。
We molecularly cloned a new Grb2 family member, named Grf40, containing the common SH3-SH2-SH3 motif. Expression of Grf40 is predominant in hematopoietic cells, particularly T cells. Grf40 binds to the SH2 domain–containing leukocyte protein of 76 kD (SLP-76) via its SH3 domain more tightly than Grb2. Incidentally, Grf40 binds to linker for activation of T cells (LAT) possibly via its SH2 domain. Overexpression of wild-type Grf40 in Jurkat cells induced a significant increase of SLP-76–dependent interleukin (IL)-2 promoter and nuclear factor of activated T cell (NF-AT) activation upon T cell receptor (TCR) stimulation, whereas the COOH-terminal SH3-deleted Grf40 mutant lacked any recognizable increase in IL-2 promoter activity. Furthermore, the SH2-deleted Grf40 mutant led to a marked inhibition of these regulatory activities, the effect of which is apparently stronger than that of the SH2-deleted Grb2 mutant. Our data suggest that Grf40 is an adaptor molecule involved in TCR-mediated signaling through a more efficient interaction than Grb2 with SLP-76 and LAT.