RRC ID 6808
Author Tanuma N, Nomura M, Ikeda M, Kasugai I, Tsubaki Y, Takagaki K, Kawamura T, Yamashita Y, Sato I, Sato M, Katakura R, Kikuchi K, Shima H.
Title Protein phosphatase Dusp26 associates with KIF3 motor and promotes N-cadherin-mediated cell-cell adhesion.
Journal Oncogene
Abstract Recent studies have demonstrated essential functions for KIF3, a microtubule-directed protein motor, in subcellular transport of several cancer-related proteins, including the beta-catenin-cadherin(s) complex. In this study, we report identification of the protein-phosphatase Dusp26 as a novel regulator of the KIF3 motor. Here we undertake yeast two-hybrid screening and identify Kif3a, a motor subunit of the KIF3 heterotrimeric complex, as a novel Dusp26-binding protein. Co-immunoprecipitation and colocalization experiments revealed that Dusp26 associates not only with Kif3a, but also with Kap3, another subunit of the KIF3 complex. Dephosphorylation experiments in vitro and analysis using mutant forms of Dusp26 in intact cells strongly suggested that Dusp26 is recruited to the KIF3 motor mainly by interaction with Kif3a, and thereby dephosphorylates Kap3. Forced expression of Dusp26, but not its catalytically inactive mutant, promoted distribution of beta-catenin/N-cadherin, an established KIF3 cargo, to cell-cell junction sites, resulting in increased cell-cell adhesiveness. We also showed that Dusp26 mRNA expression was downregulated in human glioblastoma samples. These results suggest previously unidentified functions of Dusp26 in intracellular transport and cell-cell adhesion. Downregulation of Dusp26 may contribute to malignant phenotypes of glioma.
Volume 28(5)
Pages 752-61
Published 2009-2-5
DOI 10.1038/onc.2008.431
PII onc2008431
PMID 19043453
MeSH Adaptor Proteins, Signal Transducing / metabolism Animals Brain Neoplasms / enzymology Brain Neoplasms / genetics COS Cells Cadherins / metabolism Cadherins / physiology* Cell Adhesion Cell Communication / physiology* Chlorocebus aethiops Cytoskeletal Proteins / metabolism Dual-Specificity Phosphatases / genetics Dual-Specificity Phosphatases / metabolism* Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Glioma / enzymology Glioma / genetics HeLa Cells Humans Kinesins / metabolism* Mice Mitogen-Activated Protein Kinase Phosphatases / genetics Mitogen-Activated Protein Kinase Phosphatases / metabolism* Molecular Motor Proteins / metabolism NIH 3T3 Cells Phosphorylation Protein Binding
IF 7.971
Times Cited 36
Human and Animal Cells IMR-32(RCB1895)