Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Antigens, CD / metabolism
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Apoptosis
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Binding, Competitive
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Catalytic Domain
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Chemotaxis, Leukocyte
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Cytokines*
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Humans
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Interleukin-8 / metabolism*
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Interleukin-8 / pharmacology
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Leukocyte Elastase / metabolism
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Molecular Sequence Data
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Monocytes / physiology
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Neoplasm Proteins / metabolism*
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Neoplasm Proteins / pharmacology
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Neutrophils / metabolism
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Neutrophils / physiology
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RNA-Binding Proteins / metabolism*
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RNA-Binding Proteins / pharmacology
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Receptors, Interleukin / metabolism
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Receptors, Interleukin-8A
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Recombinant Proteins / metabolism
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Signal Transduction
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Tumor Cells, Cultured
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Tyrosine-tRNA Ligase / chemistry
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Tyrosine-tRNA Ligase / metabolism*
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Tyrosine-tRNA Ligase / pharmacology
Substances
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Antigens, CD
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Cytokines
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Interleukin-8
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Neoplasm Proteins
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RNA-Binding Proteins
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Receptors, Interleukin
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Receptors, Interleukin-8A
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Recombinant Proteins
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small inducible cytokine subfamily E, member 1
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Leukocyte Elastase
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Tyrosine-tRNA Ligase