Secreted human glycyl-tRNA synthetase implicated in defense against ERK-activated tumorigenesis
| Autor: | Xiang-Lei Yang, Yun Jung Park, Jung Min Han, Sunghoon Kim, Min Chul Park, Kiwon Cho, Weiwei He, Paul Schimmel, Sang Bum Kim, Da Jin, Young Woo Park, Taehee Kang, Min Guo |
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| Rok vydání: | 2012 |
| Předmět: |
Glycine-tRNA Ligase
MAPK/ERK pathway Fas Ligand Protein Apoptosis Receptors Cell Surface Tumor initiation Biology Fas ligand Dephosphorylation Mice Enzyme activator Stress Physiological Cell Line Tumor Animals Humans Phosphorylation Extracellular Signal-Regulated MAP Kinases Multidisciplinary Cadherin Macrophages fungi Protein phosphatase 2 Cadherins Xenograft Model Antitumor Assays Cell biology Enzyme Activation Mice Inbred C57BL Cell Transformation Neoplastic PNAS Plus Protein Binding |
| Zdroj: | Proceedings of the National Academy of Sciences. 109 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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