Structural separation of different extracellular activities in aminoacyl-tRNA synthetase-interacting multi-functional protein, p43/AIMP1.
AIMP1 (previously known as p43) is first found as a factor associated with a macromolecular tRNA synthetase complex. However, it is also secreted and acts on diverse target cells such as endothelial cells, macrophages, and fibroblasts to control angiogenesis, inflammation, and dermal regeneration, respectively. We previously showed that AIMP1 induces the death of endothelial cell but proliferation of fibroblasts and activates macrophages. In this work, we found that elastase 2-cleaved AIMP1 retained its pro-apoptotic activity to endothelial cells but lost the growth-stimulatory activity to fibroblasts. To determine the functional domains responsible for each activity, we generated several deletion fragments of AIMP1 and compared the activities to the target cells. AIMP1 promoted endothelial cell death and caspase-3 activation through its 101-114 amino acid region, fibroblast proliferation through its 6-46 amino acid region, and endothelial migration through its 114-192 amino acid region as revealed by deletion mapping. Thus, this work revealed that AIMP1 uses different regions for its diverse extracellular activities.
Han
Jung Min
JM
Imagene Co. Biotechnology Incubating Center, Golden Helix, Seoul National University, Seoul 151-741, Republic of Korea.
Park
Sang Gyu
SG
Lee
Yeonsook
Y
Kim
Sunghoon
S
D000595:Amino Acid Sequence; D000604:Amino Acyl-tRNA Synthetases / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D017353:Gene Deletion; D015870:Gene Expression; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism
D016207:Cytokines; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D016601:RNA-Binding Proteins; C077219:small inducible cytokine subfamily E, member 1; D012697:Serine Endopeptidases; C117309:pancreatic elastase II; D000604:Amino Acyl-tRNA Synthetases