Two distinct cytokines released from a human aminoacyl-tRNA synthetase.
Aminoacyl-tRNA synthetases catalyze aminoacylation of transfer RNAs (tRNAs). It is shown that human tyrosyl-tRNA synthetase can be split into two fragments with distinct cytokine activities. The endothelial monocyte-activating polypeptide II-like carboxy-terminal domain has potent leukocyte and monocyte chemotaxis activity and stimulates production of myeloperoxidase, tumor necrosis factor-alpha, and tissue factor. The catalytic amino-terminal domain binds to the interleukin-8 type A receptor and functions as an interleukin-8-like cytokine. Under apoptotic conditions in cell culture, the full-length enzyme is secreted, and the two cytokine activities can be generated by leukocyte elastase, an extracellular protease. Secretion of this tRNA synthetase may contribute to apoptosis both by arresting translation and producing needed cytokines.
Wakasugi
K
K
The Skaggs Institute for Chemical Biology, The Scripps Research Institute, Beckman Center, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Schimmel
P
P
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis; D001667:Binding, Competitive; D020134:Catalytic Domain; D002634:Chemotaxis, Leukocyte; D016207:Cytokines; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism* / Q000494:pharmacology; D019272:Leukocyte Elastase / Q000378:metabolism; D008969:Molecular Sequence Data; D009000:Monocytes / Q000502:physiology; D009363:Neoplasm Proteins / Q000378:metabolism* / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology; D016601:RNA-Binding Proteins / Q000378:metabolism* / Q000494:pharmacology; D018123:Receptors, Interleukin / Q000378:metabolism; D023062:Receptors, Interleukin-8A; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014448:Tyrosine-tRNA Ligase / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
D015703:Antigens, CD; D016207:Cytokines; D016209:Interleukin-8; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A; D011994:Recombinant Proteins; C077219:small inducible cytokine subfamily E, member 1; D019272:Leukocyte Elastase; D014448:Tyrosine-tRNA Ligase