title: Identification of CD23 as a functional receptor for the proinflammatory cytokine AIMP1/p43.
abstract: Aminoacyl-tRNA-synthetase-interacting multifunctional protein 1 (AIMP1/p43) can be secreted to trigger proinflammatory molecules while it is predominantly bound to a cytoplasmic macromolecular protein complex that contains several different aminoacyl-tRNA synthetases. Although its activities as a secreted signaling factor have been well characterized, the functional receptor for its proinflammatory activity has not yet identified. In this study, we have identified the receptor molecule for AIMP1 that mediates the secretion of TNF-α from THP-1 monocytic cells and primary human peripheral blood mononuclear cells (PBMCs). In a screen of 499 soluble receptors we identified CD23, a known low-affinity receptor for IgE, as a high affinity binding partner of AIMP1. We found that downregulation of CD23 attenuated AIMP1-induced TNF-α secretion and AIMP1 binding to THP-1 and PBMCs. We also observed that in THP-1 and PBMCs, AIMP1-induced TNF-α secretion, mediated by CD23, involved activation of ERK1/2. Interestingly, endothelial monocyte activating polypeptide II (EMAP II), the C-terminal fragment of AIMP1 that is also known to work as a proinflammatory cytokine, was incapable of binding to CD23 and of activating ERK1/2. Therefore, identification of CD23 not only explains the inflammatory function of AIMP1 but also provides the first evidence by which the mode of action of AIMP1 can be distinguished from that of its C-terminal domain, EMAP II.
authors: Medicinal Bioconvergence Research Center, Seoul National University, Seoul 151-742,  Korea.
authors: Hyuk-Sang
authors: HS
authors: Kwon
authors: Min Chul
authors: MC
authors: Park
authors: Dae Gyu
authors: DG
authors: Kim
authors: Kiwon
authors: K
authors: Cho
authors: Young Woo
authors: YW
authors: Park
authors: Jung Min
authors: JM
authors: Han
authors: Sunghoon
authors: S
authors: Kim
mesh_terms: D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement; D016207:Cytokines / Q000737:chemistry / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D017455:Receptors, IgE / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; D017455:Receptors, IgE; D014409:Tumor Necrosis Factor-alpha; C077219:small inducible cytokine subfamily E, member 1; D048049:Extracellular Signal-Regulated MAP Kinases