A new Rac target POSH is an SHS-containing scaffold protein involved in the JNK and NF-κB signalling pathways
A new Rac target POSH is an SHS-containing scaffold protein involved in the JNK and NF-κB signalling pathways
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DOI：
10.1093/emboj/17.5.1395
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发表时间：
1998-03-02
期刊：
影响因子：
11.4
通讯作者：
Hall, A
中科院分区：
文献类型：
--
作者：
Tapon, N;Nagata, K;Hall, A
Rho， Pac和Cdc42 gtpase协调调节肌动蛋白细胞骨架和JNK MAP激酶途径的组织。先前对Rac的突变分析表明，这两种活性是由不同的细胞靶点介导的，尽管它们的身份尚不清楚。两个Pac靶点p65（PAK）和MLK是丝氨酸/苏氨酸激酶，据报道能够激活JNK通路。我们提出的证据表明，在Cos-1细胞中，Pac靶点都不是介导JNK激活的。我们利用酵母双杂交选择，鉴定了Pac的新靶点POSH。该蛋白由四个SH3结构域组成，异位表达导致JNK通路的激活和NF-kappa b的核易位。当在成纤维细胞中过度表达时，POSH是一种强诱导细胞凋亡的物质。我们认为POSH作为一种支架蛋白，参与pac诱导的信号转导通路，导致多种基因转录变化。
The Rho, Pac and Cdc42 GTPases coordinately regulate the organization of the actin cytoskeleton and the JNK MAP kinase pathway. Mutational analysis of Rac has previously shown that these two activities are mediated by distinct cellular targets, though their identity is not known. Two Pac targets, p65(PAK) and MLK, are ser/thr kinases that have been reported to be capable of activating the JNK pathway. We present evidence that neither is the Pac target mediating JNK activation in Cos-1 cells, We have used yeast two-hybrid selection and identified a new target of Pac, POSH. This protein consists of four SH3 domains and ectopic expression leads to the activation of the JNK pathway and to nuclear translocation of NF-kappa B. When overexpressed in fibroblasts, POSH is a strong inducer of apoptosis. We propose that POSH acts as a scaffold protein and contributes to Pac-induced signal transduction pathways leading to diverse gene transcriptional changes.