Precursor of pro-apoptotic cytokine modulates aminoacylation activity of tRNA synthetase.
Endothelial monocyte activating polypeptide II (EMAPII) is a cytokine that is specifically induced by apoptosis. Its precursor (pro-EMAPII) has been suggested to be identical to p43, which is associated with the multi-tRNA synthetase complex. Herein, we have demonstrated that the N-terminal domain of pro-EMAPII interacts with the N-terminal extension of human cytoplasmic arginyl-tRNA synthetase (RRS) using genetic and immunoprecipitation analyses. Aminoacylation activity of RRS was enhanced about 2.5-fold by the interaction with pro-EMAPII but not with its N- or C-terminal domains alone. The N-terminal extension of RRS was not required for enzyme activity but did mediate activity stimulation by pro-EMAPII. Pro-EMAPII reduced the apparent Km of RRS to tRNA, whereas the kcat value remained unchanged. Therefore, the precursor of EMAPII is a multi-functional protein that assists aminoacylation in normal cells and releases the functional cytokine upon apoptosis.
Park
S G
SG
National Creative Research Initiatives Center for ARS Network, Sung Kyun Kwan University, Suwon, Kyunggido, 440-746, Korea.
Jung
K H
KH
Lee
J S
JS
Jo
Y J
YJ
Motegi
H
H
Kim
S
S
Shiba
K
K
D000215:Acylation; D000595:Amino Acid Sequence; D017209:Apoptosis; D001126:Arginine-tRNA Ligase / Q000378:metabolism*; D003001:Cloning, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding
D010446:Peptide Fragments; D001126:Arginine-tRNA Ligase