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研究発表を行った学会；
・オリジナルデータ

タイトル；Pro- and anti-apoptotic dual functions of the C5a receptor: Involvement of Regulator of G protein Signaling 3 and Extracellular signal-Regulated Kinase.
　
発表者；　西浦　弘志　氏
　　　（熊本大学　大学院生命科学研究部　分子病理学分野）

Abstract；
When apoptosis is initiated by manganese (II)-loading, hyperthermia or thapsigargin-treatment, human HL-60 and AsPC-1 cells initiate de novo synthesis of the C5a receptor (C5aR) and generation of its ligand, the ribosomal protein S19 (RP S19) homodimer. The ligand-receptor interaction, in an autocrine/paracrine fashion, promotes apoptosis, which can be bypassed by exogenous administration of C5a, another ligand. The proapoptotic function of the RP S19 dimer is reproduced by a C5a/RPS19 chimera that contains the body of C5a and the C-terminal region (Ile134-His145) of RP S19. The RP S19 dimer or C5a/RPS19 and C5a inversely regulate the expression of Regulator of G protein Signaling 3 (RGS3) gene in the apoptosis-initiated cells. Namely, the RP S19-type proteins up-regulate RGS3 expression, while the C5a reduce it. Transformation of HL-60 cells to over-express RGS3 promotes apoptosis in association with down-regulation of the Extracellular signal-Regulated Kinase (ERK) signal, and vice versa in the RGS3 knocked-down cells. Consistent with this result, an inhibitor of ERK phosphorylation effectively enhances the apoptotic rate in wild type HL-60 cells. Moreover, a dominant negative effect on the RP S19 dimer production encourages apoptosis-initiated HL-60 cells with a longer life span in mouse than the natural effect. Our data indicate that, in apoptosis-initiated cells, the ligand-dependent C5aR-mediated dual signal affects the fate of cells, either apoptosis execution or survival, via regulation of RGS3 gene expression and subsequent modulation of ERK signal.