Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

PNAS 109 (11): 640-647

Copyright © 2012 by the National Academy of Sciences.

PNAS Plus


PNAS PLUS / BIOLOGICAL SCIENCES / CELL BIOLOGY

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

Min Chul Parka, Taehee Kanga, Da Jina, Jung Min Hana, Sang Bum Kima, Yun Jung Parkb, Kiwon Chob, Young Woo Parkb, Min Guoc, Weiwei Hed, Xiang-Lei Yangd, Paul Schimmeld,1, and Sunghoon Kima,e,1

aMedicinal Bioconvergence Research Center, and eWorld Class University Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Technology, Seoul National University, Seoul 151-742, Korea; bIntegrative Omics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea; cDepartment of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458; and dThe Skaggs Institute for Chemical Biology and Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037

1To whom correspondence may be addressed. E-mail: schimmel{at}scripps.edu or sungkim{at}snu.ac.kr.

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.

Key Words: cytokine • proapoptotic effect • immune surveillance • cancer microenvironment


 

The authors declare no conflict of interest.

This is a Contributed submission.

See full research article on page E640 of www.pnas.org.

Cite this Author Summary as: PNAS 10.1073/pnas.1200194109.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Aminoacyl-tRNA synthetases in medicine and disease.
P. Yao and P. L. Fox (2013)
EMBO Mol Med. 5, 332-343
   Abstract »    Full Text »    PDF »
Identification of CD23 as a functional receptor for the proinflammatory cytokine AIMP1/p43.
H.-S. Kwon, M. C. Park, D. G. Kim, K. Cho, Y. W. Park, J. M. Han, and S. Kim (2012)
J. Cell Sci. 125, 4620-4629
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882