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In mammalian cells, specific aminoacyl-transfer RNA (tRNA) synthetases have cytokine functions that require interactions with partners outside of the translation apparatus. Little is known about these interactions and how they facilitate expanded functions that link protein translation to other cellular pathways. For example, an alternative splice fragment of tryptophanyl-tRNA synthetase (TrpRS) and a similar natural proteolytic fragment are potent angiostatic factors that act through the vascular endothelial-cadherin receptor and Akt signaling pathway. Here we demonstrate mobilization of TrpRS for exocytosis from endothelial cells and the potential for plasmin to activate the cytokine function of the extracellular synthetase. Direct physical evidence showed that the annexin II-S100A10 complex, which regulates exocytosis, forms a ternary complex with TrpRS. Functional studies demonstrate that both annexin II and S100A10 regulate trafficking of TrpRS. Thus, complexes of mammalian tRNA synthetases with seemingly disparate proteins may in general be relevant to understanding how their expanded functions are implemented.

Original publication

DOI

10.1074/jbc.M706028200

Type

Journal article

Journal

J Biol Chem

Publication Date

25/01/2008

Volume

283

Pages

2070 - 2077

Keywords

Alternative Splicing, Angiostatic Proteins, Annexin A2, Cells, Cultured, Cytokines, Endothelial Cells, Exocytosis, Fibrinolysin, Humans, Multiprotein Complexes, Protein Biosynthesis, Protein Transport, Proto-Oncogene Proteins c-akt, S100 Proteins, Signal Transduction, Tryptophan-tRNA Ligase