Structural separation of different extracellular activities in aminoacyl-tRNA synthetase-interacting multi-functional protein, p43/AIMP1

Biochem Biophys Res Commun. 2006 Mar 31;342(1):113-8. doi: 10.1016/j.bbrc.2006.01.117. Epub 2006 Feb 2.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acyl-tRNA Synthetases / metabolism*
  • Animals
  • Cattle
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Cytokines / chemistry*
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Endothelial Cells / chemistry
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism
  • Gene Deletion
  • Gene Expression
  • Molecular Sequence Data
  • Mutation / genetics
  • Neoplasm Proteins / chemistry*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Protein Binding
  • RNA-Binding Proteins / chemistry*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Serine Endopeptidases / metabolism

Substances

  • Cytokines
  • Neoplasm Proteins
  • Peptide Fragments
  • RNA-Binding Proteins
  • small inducible cytokine subfamily E, member 1
  • Serine Endopeptidases
  • pancreatic elastase II
  • Amino Acyl-tRNA Synthetases