Evidence for annexin II-S100A10 complex and plasmin in mobilization of cytokine activity of human TrpRS.
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.
Kapoor
Mili
M
Department of Molecular Biology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Zhou
Quansheng
Q
Otero
Francella
F
Myers
Christopher A
CA
Bates
Alison
A
Belani
Rajesh
R
Liu
Jianming
J
Luo
Jiann-Kae
JK
Tzima
Eleni
E
Zhang
Dong-Er
DE
Yang
Xiang-Lei
XL
Schimmel
Paul
P
D017398:Alternative Splicing / Q000502:physiology; D043165:Angiostatic Proteins / Q000235:genetics / Q000378:metabolism*; D017306:Annexin A2 / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D005089:Exocytosis / Q000502:physiology; D005341:Fibrinolysin / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014369:Tryptophan-tRNA Ligase / Q000235:genetics / Q000378:metabolism*; D000099248:S100 Calcium Binding Protein A10
D043165:Angiostatic Proteins; D017306:Annexin A2; D016207:Cytokines; D005341:Fibrinolysin; D046912:Multiprotein Complexes; D051057:Proto-Oncogene Proteins c-akt; D009418:S100 Proteins; D014369:Tryptophan-tRNA Ligase; D000099248:S100 Calcium Binding Protein A10