Identification of the PAK4 interactome reveals PAK4 phosphorylation of N-WASP and promotion of Arp2/3-dependent actin polymerization
| Autor: | Matthias Spiess, Miao Zhao, Staffan Strömblad, Henrik J. Johansson, Jianjiang Hu, Helene Olofsson, Janne Lehtiö |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
VCA domain actin cytoskeleton Cell growth Kinase macromolecular substances Biology Actin cytoskeleton Interactome Protein–protein interaction Cell biology protein-protein interaction 03 medical and health sciences 030104 developmental biology Oncology Proteasome p21-activated kinase 4 Phosphorylation Actin Research Paper mass spectrometry |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | p21-activated kinase 4 (PAK4) regulates cell proliferation, apoptosis, cell motility and F-actin remodeling, but the PAK4 interactome has not been systematically analyzed. Here, we comprehensively characterized the human PAK4 interactome by iTRAQ quantitative mass spectrometry of PAK4-immunoprecipitations. Consistent with its multiple reported functions, the PAK4 interactome was enriched in diverse protein networks, including the 14-3-3, proteasome, replication fork, CCT and Arp2/3 complexes. Because PAK4 co-immunoprecipitated most subunits of the Arp2/3 complex, we hypothesized that PAK4 may play a role in Arp2/3 dependent actin regulation. Indeed, we found that PAK4 interacts with and phosphorylates the nucleation promoting factor N-WASP at Ser484/Ser485 and promotes Arp2/3-dependent actin polymerization in vitro. Also, PAK4 ablation in vivo reduced N-WASP Ser484/Ser485 phosphorylation and altered the cellular balance between G- and F-actin as well as the actin organization. By presenting the PAK4 interactome, we here provide a powerful resource for further investigations and as proof of principle, we also indicate a novel mechanism by which PAK4 regulates actin cytoskeleton remodeling. |
| Databáze: | OpenAIRE |
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