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	Min Chul Park, Taehee Kang, Da Jin, Jung Min Han, Sang Bum Kim, Yun Jung Park, Kiwon Cho, Young Woo Park, Min Guo, Weiwei He, Xiang-Lei Yang, Paul Schimmel, Sunghoon Kim
Journal	Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 109 Issue 11 Pg. E640-7 (Mar 13 2012) ISSN: 1091-6490 [Electronic] United States
PMID	22345558 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Cadherins Fas Ligand Protein Receptors, Cell Surface Extracellular Signal-Regulated MAP Kinases Glycine-tRNA Ligase K cadherin
Topics	Animals Apoptosis Cadherins (metabolism) Cell Line, Tumor Cell Transformation, Neoplastic (immunology, pathology) Enzyme Activation Extracellular Signal-Regulated MAP Kinases (metabolism) Fas Ligand Protein (metabolism) Glycine-tRNA Ligase (metabolism) Humans Macrophages (enzymology) Mice Mice, Inbred C57BL Phosphorylation Protein Binding Receptors, Cell Surface (metabolism) Stress, Physiological Xenograft Model Antitumor Assays

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