RIBP, a novel Rlk/Txk- and itk-binding adaptor protein that regulates T cell activation.
RIBP, a novel Rlk/Txk- and itk-binding adaptor protein that regulates T cell activation.
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DOI：
10.1084/jem.190.11.1657
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发表时间：
1999-12-06
期刊：
影响因子：
--
通讯作者：
Bluestone JA
中科院分区：
文献类型：
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作者：
Rajagopal K;Sommers CL;Decker DC;Mitchell EO;Korthauer U;Sperling AI;Kozak CA;Love PE;Bluestone JA
在小鼠T细胞淋巴瘤文库的酵母双杂交筛选中，基于其结合Rlk/Txk的能力，鉴定了一种新的T细胞特异性衔接蛋白RIBP。还发现RIBP与酪氨酸激酶Tec家族的相关成员Itk相互作用。RIBP的表达仅限于T细胞和自然杀伤细胞，并且在T细胞活化后显著上调。RIBP破坏敲除小鼠显示出明显正常的T细胞发育。然而，响应于T细胞受体（TCR）介导的活化的RIBP缺陷型T细胞的增殖显著受损。此外，这些活化的T细胞在产生白细胞介素（IL）-2和干扰素γ方面有缺陷，但不产生IL-4。这些数据表明RIBP在TCR介导的信号转导途径中起重要作用，并且其与Itk和Rlk/Txk的结合可以调节T细胞分化。
A novel T cell–specific adaptor protein, RIBP, was identified based on its ability to bind Rlk/Txk in a yeast two-hybrid screen of a mouse T cell lymphoma library. RIBP was also found to interact with a related member of the Tec family of tyrosine kinases, Itk. Expression of RIBP is restricted to T and natural killer cells and is upregulated substantially after T cell activation. RIBP-disrupted knockout mice displayed apparently normal T cell development. However, proliferation of RIBP-deficient T cells in response to T cell receptor (TCR)-mediated activation was significantly impaired. Furthermore, these activated T cells were defective in the production of interleukin (IL)-2 and interferon γ, but not IL-4. These data suggest that RIBP plays an important role in TCR-mediated signal transduction pathways and that its binding to Itk and Rlk/Txk may regulate T cell differentiation.