Rap1a deficiency modifies cytokine responses and MAPK-signaling in vitro and impairs the in vivo inflammatory response
Rap1a deficiency modifies cytokine responses and MAPK-signaling in vitro and impairs the in vivo inflammatory response
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DOI：
10.1016/j.cellimm.2012.05.008
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发表时间：
2012-03-01
影响因子：
4.3
通讯作者：
Scheele, Juergen S.
中科院分区：
文献类型：
--
作者：
Dorn, Annette;Zoellner, Anna;Scheele, Juergen S.
Rap1与ras密切相关，在t细胞受体（TCR）信号传导中起关键作用。没有共刺激的tcr刺激会导致rap1组成性激活，rap1可能通过抑制ras依赖的细胞外信号调节激酶（ERK）诱导来介导t细胞的能量。这种激活是由第二种蛋白激酶b-Raf介导的。Rap1-GIP被认为通过结合b-raf以ras无关的方式激活ERK。一般来说，T细胞不表达b-rat，但它们表达接头蛋白raf-1，该蛋白通常被rapt隔离，导致ras介导的ERK活化受到抑制。在这项研究中，我们证明了在rap1缺失的T细胞中，ERK和p38激酶的信号在不同刺激激活后增加，导致细胞内积累和细胞因子的分泌增加。此外，在一个超敏模型中，rap1缺失小鼠比野生型小鼠表现出更少的接触性皮炎，证明rap1缺失对体内炎症反应的影响。(C) 2012爱思唯尔公司版权所有。
Rap1, which is closely related to ras, plays a key role in T-cell receptor (TCR)-signaling. TCR-stimulation without costimulation leads to constitutively activated rap1, which may mediate T-cell anergy via inhibition of ras-dependent induction of extracellular signal-regulated kinases (ERK). This activation is mediated by a second protein kinase b-Raf. Rap1-GIP is thought to activate ERK in a ras-independent manner by binding b-raf. Generally, T cells do not express b-rat while they express the adaptor protein raf-1, which is usually sequestered by rapt leading to inhibition of ras-mediated ERK activation. In this study, we demonstrate that in rap1-deficient T cells, signaling by the ERK and p38 kinases is increased following activation by different stimuli leading to increased intracellular accumulation and secretion of cytokines. In addition, in a hypersensitivity model rap1-deficient mice demonstrated reduced contact dermatitis compared to wildtype mice, demonstrating the impact of rap1-deficiency on the inflammatory response in vivo. (C) 2012 Elsevier Inc. All rights reserved.