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Nore1B regulates TCR signaling via Ras and Carma1

机译:Nore1B通过Ras和Carma1调节TCR信号传导

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摘要

Nore1A was originally identified as a potential Ras effector, and Nore1B is an alternatively spliced isoform. Both share a Ras/Rap association domain (RA domain) but only Nore1A contains sequence motifs that predict SH3 domain binding and diacylglycerol/phorbol ester binding in the amino-terminal region. Here we report that Carma1 binds to Nore1A and Nore1B through the RA domain and that Carma1 interacts with active Ras in the presence of Note1B. RNA interference against Nore1B attenuates NF-kappa B activation induced by T cell receptor (TCR) ligation, but not NF-kappa B activation induced by TNF alpha or lipoteichoic acid. In addition, Nore1B is also required for KiRas GV12-mediated ERK1 activation and Elk1 reporter activity in T cells. We also provide evidence that knockdown of Nore1B also impairs polarized redistribution of Ras at the B cell-T cell immune interface. Together, these findings suggest that endogenous Nore1B recruits active Ras to the APC-T cell interface and mediates the interaction between Ras and Carma1. (c) 2006 Elsevier Inc. All rights reserved.
机译:Nore1A最初被确定为潜在的Ras效应子,而Nore1B是另一种剪接的同工型。两者都共享一个Ras / Rap缔合域(RA域),但只有Nore1A含有预测氨基端区域中SH3域结合和二酰基甘油/佛波醇酯结合的序列基序。在这里,我们报告Carma1通过RA域与Nore1A和Nore1B结合,并且在Note1B存在的情况下Carma1与活性Ras相互作用。 RNA对Nore1B的干扰会减弱T细胞受体(TCR)连接诱导的NF-κB活化,但不能减弱TNFα或脂蛋白酸诱导的NF-κB活化。此外,Kires GV12介导的ERK1激活和T细胞中Elk1报告基因活性也需要Nore1B。我们还提供证据表明,敲除Nore1B还会损害Ras在B细胞-T细胞免疫界面的极化再分布。总之,这些发现表明内源性Nore1B将活跃的Ras募集到APC-T细胞界面,并介导Ras与Carma1之间的相互作用。 (c)2006 Elsevier Inc.保留所有权利。

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