title: Interaction of two translational components, lysyl-tRNA synthetase and p40/37LRP, in plasma membrane promotes laminin-dependent cell migration.
abstract: Although human lysyl-tRNA synthetase (KRS), an enzyme for protein synthesis, is often highly expressed in various cancer cells, its pathophysiological implications have not been understood. Here we found that KRS induces cancer cell migration through interaction with the 67-kDa laminin receptor (67LR) that is converted from ribosomal subunit p40. On laminin signal, KRS was phosphorylated at the T52 residue by p38MAPK and dissociated from the cytosolic multi-tRNA synthetase complex for membrane translocation. The importance of T52 phosphorylation for membrane translocation of KRS was confirmed by site-directed mutagenesis. In the membrane, turnover of 67LR was controlled by Nedd4-mediated ubiquitination, and KRS inhibited ubiquitin-dependent degradation of 67LR, thereby enhancing laminin-induced cell migration. This work thus unveiled a unique function of KRS in the control of cell migration and its pathological implication in metastasis.
authors: Medicinal Bioconvergence Research Center, College of Pharmacy, World Class University Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul National University, Seoul 151-742, Korea.
authors: Dae Gyu
authors: DG
authors: Kim
authors: Jin Woo
authors: JW
authors: Choi
authors: Jin Young
authors: JY
authors: Lee
authors: Hyerim
authors: H
authors: Kim
authors: Young Sun
authors: YS
authors: Oh
authors: Jung Weon
authors: JW
authors: Lee
authors: Yu Kyung
authors: YK
authors: Tak
authors: Joon Myong
authors: JM
authors: Song
authors: Ehud
authors: E
authors: Razin
authors: Seok-Hyun
authors: SH
authors: Yun
authors: Sunghoon
authors: S
authors: Kim
mesh_terms: D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D007797:Laminin / Q000494:pharmacology*; D008250:Lysine-tRNA Ligase / Q000235:genetics / Q000378:metabolism*; D013058:Mass Spectrometry; D010766:Phosphorylation / Q000187:drug effects; D017474:Receptors, Laminin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D054682:Ribosome Subunits, Small, Eukaryotic / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D054875:Ubiquitination
chemical_list: D007797:Laminin; D017474:Receptors, Laminin; D008250:Lysine-tRNA Ligase