title: Arg kinase-binding protein 2 (ArgBP2) interaction with α-actinin and actin stress fibers inhibits cell migration.
abstract: Cell migration requires dynamic remodeling of the actomyosin network. We report here that an adapter protein, ArgBP2, is a component of α-actinin containing stress fibers and inhibits migration. ArgBP2 is undetectable in many commonly studied cancer-derived cell lines. COS-7 and HeLa cells express ArgBP2 (by Western analysis), but expression was detectable only in approximately half the cells by immunofluorescence. Short term clonal analysis demonstrated 0.2-0.3% of cells switch ArgBP2 expression (on or off) per cell division. ArgBP2 can have a fundamental impact on the actomyosin network: ArgBP2 positive COS-7 cells, for example, are clearly distinguishable by their denser actomyosin (stress fiber) network. ArgBP2γ binding to α-actinin appears to underlie its ability to localize to stress fibers and decrease cell migration. We map a small α-actinin binding region in ArgBP2 (residues 192-228) that is essential for these effects. Protein kinase A phosphorylation of ArgBP2γ at neighboring Ser-259 and consequent 14-3-3 binding blocks its interaction with α-actinin. ArgBP2 is known to be down-regulated in some aggressively metastatic cancers. Our work provides a biochemical explanation for the anti-migratory effect of ArgBP2.
authors.affiliation: From the sGSK Group Institute of Molecular and Cell Biology (IMCB), Proteos Building, 61 Biopolis Drive, 138673 Singapore.
authors.forename: Praju Vikas
authors.initials: PV
authors.lastname: Anekal
authors.affiliation: From the sGSK Group Institute of Molecular and Cell Biology (IMCB), Proteos Building, 61 Biopolis Drive, 138673 Singapore.
authors.forename: Jeffery
authors.initials: J
authors.lastname: Yong
authors.affiliation: From the sGSK Group Institute of Molecular and Cell Biology (IMCB), Proteos Building, 61 Biopolis Drive, 138673 Singapore, the Institute of Medical Biology (IMB), 8A Biomedical Grove, 06-06 Immunos Building, 138648 Singapore, and the Department of Pharmacology, National University of Singapore, 119077 Singapore ed.manser@imb.a-star.edu.sg.
authors.forename: Ed
authors.initials: E
authors.lastname: Manser
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism; D000185:Actinin / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000205:Actomyosin / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019556:COS Cells; D045744:Cell Line, Tumor; D002465:Cell Movement; D002522:Chlorocebus aethiops; D005576:Colforsin / Q000737:chemistry; D003599:Cytoskeleton / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D008856:Microscopy, Fluorescence; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D011485:Protein Binding; D016601:RNA-Binding Proteins; D014162:Transfection
chemical_list: D048948:14-3-3 Proteins; D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D018398:Homeodomain Proteins; D016601:RNA-Binding Proteins; C490755:SORBS2 protein, human; D000185:Actinin; D005576:Colforsin; D000205:Actomyosin
keywords: 14-3-3 Protein; Actin Stress Fibers; Actinin; ArgBP2; Cell Migration; Cytoskeleton; Protein kinase A (PKA); Tumor Metastasis