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Title 

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

Authors 

M C ParkT KangD JinJ M HanS B KimY J ParkK ChoYoung Woo ParkM GuoW HeX L YangP SchimmelS Kim

Publisher 

National Academy of Sciences

Issue Date 

2012

Citation 

Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 11, pp. E640-E647

Keywords 

Cancer microenvironmentCytokineImmune surveillanceProapoptotic effect

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.

ISSN 

0027-8424

Link 

http://dx.doi.org/10.1073/pnas.1200194109

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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