TY - JOUR
T1 - Secreted human glycyl-tRNA synthetase implicated in defense against ERK-activated tumorigenesis
AU - Park, Min Chul
AU - Kang, Taehee
AU - Jin, Da
AU - Han, Jung Min
AU - Kim, Sang Bum
AU - Park, Yun Jung
AU - Cho, Kiwon
AU - Park, Young Woo
AU - Guo, Min
AU - He, Weiwei
AU - Yang, Xiang Lei
AU - Schimmel, Paul
AU - Kim, Sunghoon
PY - 2012/3/13
Y1 - 2012/3/13
N2 - 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.
AB - 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.
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U2 - 10.1073/pnas.1200194109
DO - 10.1073/pnas.1200194109
M3 - Article
C2 - 22345558
AN - SCOPUS:84863251058
SN - 0027-8424
VL - 109
SP - E640-E647
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 11
ER -