Evidence for Annexin II-S100A10 Complex and Plasmin in Mobilization of Cytokine Activity of Human TrpRS

• Published in: The Journal of biological chemistry Vol. 283; no. 4; pp. 2070 - 2077
• Main Authors: Kapoor, Mili, Zhou, Quansheng, Otero, Francella, Myers, Christopher A., Bates, Alison, Belani, Rajesh, Liu, Jianming, Luo, Jiann-Kae, Tzima, Eleni, Zhang, Dong-Er, Yang, Xiang-Lei, Schimmel, Paul
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25.01.2008; American Society for Biochemistry and Molecular Biology
• Subjects: Alternative Splicing - physiology; Angiostatic Proteins - genetics; Angiostatic Proteins - metabolism; Annexin A2 - genetics; Annexin A2 - metabolism; Cells, Cultured; Cytokines - genetics; Cytokines - metabolism; Endothelial Cells - cytology; Endothelial Cells - metabolism; Exocytosis - physiology; Fibrinolysin - genetics; Fibrinolysin - metabolism; Humans; Multiprotein Complexes - genetics; Multiprotein Complexes - metabolism; Protein Biosynthesis - physiology; Protein Transport - physiology; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; S100 Proteins - genetics; S100 Proteins - metabolism; Signal Transduction - physiology; Tryptophan-tRNA Ligase - genetics; Tryptophan-tRNA Ligase - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M706028200

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.