title: Secreted human glycyl-tRNA synthetase implicated in defense against ERK-activated tumorigenesis.
abstract: Although adaptive systems of immunity against tumor initiation and destruction are well investigated, less understood is the role, if any, of endogenous factors that have conventional functions. Here we show that glycyl-tRNA synthetase (GRS), an essential component of the translation apparatus, circulates in serum and can be secreted from macrophages in response to Fas ligand that is released from tumor cells. Through cadherin (CDH)6 (K-cadherin), GRS bound to different ERK-activated tumor cells, and released phosphatase 2A (PP2A) from CDH6. The activated PP2A then suppressed ERK signaling through dephosphorylation of ERK and induced apoptosis. These activities were inhibited by blocking GRS with a soluble fragment of CDH6. With in vivo administration of GRS, growth of tumors with a high level of CDH6 and ERK activation were strongly suppressed. Our results implicate a conventional cytoplasmic enzyme in translation as an intrinsic component of the defense against ERK-activated tumor formation.
authors.affiliation: Medicinal Bioconvergence Research Center, and World Class University Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Technology,  Seoul National University, Seoul 151-742,  Korea.
authors.forename: Min Chul
authors.initials: MC
authors.lastname: Park
authors.forename: Taehee
authors.initials: T
authors.lastname: Kang
authors.forename: Da
authors.initials: D
authors.lastname: Jin
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Han
authors.forename: Sang Bum
authors.initials: SB
authors.lastname: Kim
authors.forename: Yun Jung
authors.initials: YJ
authors.lastname: Park
authors.forename: Kiwon
authors.initials: K
authors.lastname: Cho
authors.forename: Young Woo
authors.initials: YW
authors.lastname: Park
authors.forename: Min
authors.initials: M
authors.lastname: Guo
authors.forename: Weiwei
authors.initials: W
authors.lastname: He
authors.forename: Xiang-Lei
authors.initials: XL
authors.lastname: Yang
authors.forename: Paul
authors.initials: P
authors.lastname: Schimmel
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000276:immunology* / Q000473:pathology*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D053222:Fas Ligand Protein / Q000378:metabolism; D006032:Glycine-tRNA Ligase / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism; D013312:Stress, Physiological; D023041:Xenograft Model Antitumor Assays
chemical_list: D015820:Cadherins; D053222:Fas Ligand Protein; D011956:Receptors, Cell Surface; D048049:Extracellular Signal-Regulated MAP Kinases; D006032:Glycine-tRNA Ligase; C087310:K cadherin