Scaffolding function of PAK in the PDK1-Akt pathway
Scaffolding function of PAK in the PDK1-Akt pathway
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DOI：
10.1038/ncb1795
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发表时间：
2008-11-01
影响因子：
21.3
通讯作者：
Gotoh, Yukiko
中科院分区：
文献类型：
--
作者：
Higuchi, Maiko;Onishi, Keisuke;Gotoh, Yukiko
许多细胞外信号刺激磷脂酰肌醇-3-激酶，磷脂酰肌醇-3-激酶进而激活Rac 1 GT3、蛋白激酶Akt和Akt Thr 308上游激酶PDK 1。活性Rac 1刺激许多事件，包括PAK激酶家族亚组的底物磷酸化。Rac 1、PDK 1和Akt的联合作用对细胞迁移、生长、存活、代谢和肿瘤发生至关重要。在这里，我们表明，Rac 1刺激第二，激酶独立的功能PAK 1。PAK 1激酶结构域作为支架，促进PDK 1刺激Akt并帮助Akt募集到膜上。PAK差异性激活Akt亚群。这些发现揭示了PAK调节PDK 1-Akt通路的效率、定位和特异性的支架功能。
Many extracellular signals stimulate phosphatidylinositol-3- kinase, which in turn activates the Rac1 GTPase, the protein kinase Akt and the Akt Thr 308 upstream kinase PDK1. Active Rac1 stimulates a number of events, including substrate phosphorylation by a subgroup of the PAK family of kinases. The combined effects of Rac1, PDK1 and Akt are crucial for cell migration, growth, survival, metabolism and tumorigenesis. Here we show that Rac1 stimulates a second, kinase-independent function of PAK1. The PAK1 kinase domain serves as a scaffold to facilitate Akt stimulation by PDK1 and to aid recruitment of Akt to the membrane. PAK differentially activates subpopulations of Akt. These findings reveal scaffolding functions of PAK that regulate the efficiency, localization and specificity of the PDK1-Akt pathway.