Secreted human glycyl-tRNA synthetase implicated in defense against ERK-activated tumorigenesis

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

Research output: Contribution to journalArticle

66 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)E640-E647
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number11
DOIs
Publication statusPublished - 2012 Mar 13

    Fingerprint

All Science Journal Classification (ASJC) codes

  • General

Cite this

Park, M. C., Kang, T., Jin, D., Han, J. M., Kim, S. B., Park, Y. J., Cho, K., Park, Y. W., Guo, M., He, W., Yang, X. L., Schimmel, P., & Kim, S. (2012). Secreted human glycyl-tRNA synthetase implicated in defense against ERK-activated tumorigenesis. Proceedings of the National Academy of Sciences of the United States of America, 109(11), E640-E647. https://doi.org/10.1073/pnas.1200194109