首页> 外文期刊>Cellular immunology >PICOT, protein kinase C theta-interacting protein, is a novel regulator of FcepsilonRI-mediated mast cell activation.
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PICOT, protein kinase C theta-interacting protein, is a novel regulator of FcepsilonRI-mediated mast cell activation.

机译:PICOT是蛋白激酶C theta相互作用蛋白,是FcepsilonRI介导的肥大细胞激活的新型调节剂。

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摘要

PICOT (PKC-interacting cousin of thioredoxin) consists of one thioredoxin homology domain in the N-terminal and two tandem PICOT homology domains in the C-terminal. PICOT specifically interacts with protein kinase C theta (PKC-theta) via its thioredoxin homology domain and acts as an important modulator of T cell receptor (TCR)-signaling. Using PICOT overexpressing rat basophilic leukemia cells (RBL-2H3), we evaluated the effect of PICOT overexpression on the FcepsilonRI-mediated signaling. In comparison to the control cells, introduction of PICOT to RBL-2H3 cells induced increased degranulation and the activation of NFAT and in the expression of IL-4 and TNF-alpha transcripts by FcepsilonRI-crosslinking, whereas no significant change was observed with the elevation of ERK1/2 and p38 MAP kinase phosphorylation and NF-kappaB activation by FcepsilonRI aggregation. More interesting was the exogenous PICOT overexpression in RBL-2H3 cells causing a large decrease in the elevation of JNK phosphorylation. PICOT-regulated FcepsilonRI-mediated signals in RBL-2H3 cells and acted as a positive regulator on IL-4 and TNF-alpha expression, NFAT and degranulation signal pathways and a negative regulator on a JNK signal pathway. Considering that PICOT has no enzymatic activity, the regulation of PICOT on FcepsilonRI-signaling may depend on PICOT-associated molecule(s).
机译:PICOT(硫氧还蛋白的PKC交互表亲)在N端由一个硫氧还蛋白同源结构域组成,在C端由两个串联的PICOT同源结构域组成。 PICOT通过其硫氧还蛋白同源域与蛋白激酶C theta(PKC-theta)特异性相互作用,并充当T细胞受体(TCR)信号的重要调节剂。使用PICOT过表达的大鼠嗜碱性粒细胞(RBL-2H3),我们评估了PICOT过表达对FcepsilonRI介导的信号传导的影响。与对照细胞相比,通过FcepsilonRI交联将PICOT引入RBL-2H3细胞诱导了脱粒和NFAT活化增加以及IL-4和TNF-α转录本的表达增加,而升高时未观察到明显变化。 FcepsilonRI聚集体诱导ERK1 / 2和p38 MAP激酶磷酸化和NF-κB活化。更有趣的是RBL-2H3细胞中的外源性PICOT过表达,导致JNK磷酸化水平的大幅降低。 PICOT调节RBL-2H3细胞中FcepsilonRI介导的信号,并充当IL-4和TNF-α表达,NFAT和脱粒信号途径的正调节剂,以及JNK信号途径的负调节剂。考虑到PICOT没有酶活性,因此PICOT对FcepsilonRI信号的调控可能取决于与PICOT相关的分子。

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