Evidence for annexin II/S100A10 complex and plasmin in mobilization of cytokine activity of human TrpRS

Kapoor M, Zhou Q, Otero F, Myers CA, Bates A, Belani R, Liu J, Luo JK, Tzima E, Zhang DE, Yang XL, Schimmel P
Source: J Biol Chem
Publication Date: (2008)
Issue: 283(4): 2070-7
Research Area:
Cancer Research/Cell Biology
Cells used in publication:
Endothelial, umbilical vein, human (HUVEC)
Species: human
Tissue Origin: vein
Endothelial, MV lung, human (HMVEC-L)
Species: human
Tissue Origin: lung
Species: human
Tissue Origin:
Nucleofector® I/II/2b
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 (VE)-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 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.