Letter abstract
Nature Cell Biology 10, 1356 - 1364 (2008)
Published online: 19 October 2008 | doi:10.1038/ncb1795
Scaffolding function of PAK in the PDK1–Akt pathway
Maiko Higuchi1,3, Keisuke Onishi1,3, Chikako Kikuchi1 & Yukiko Gotoh1,2
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.
- Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
- SORST Research Project, Japan Science and Technology Corporation, Tokyo, Japan.
- These authors contributed equally to this work.
Correspondence to: Yukiko Gotoh1,2 e-mail: ygotoh@iam.u-tokyo.ac.jp
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