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  • 标题:Different Pathways for Activation of Extracellular Signal-Regulated Kinase through Thromboxane A2 Receptor Isoforms
  • 本地全文:下载
  • 作者:Katsutoshi Miyosawa ; Masako Sasaki ; Satoko Ohkubo
  • 期刊名称:Biological and Pharmaceutical Bulletin
  • 印刷版ISSN:0918-6158
  • 电子版ISSN:1347-5215
  • 出版年度:2006
  • 卷号:29
  • 期号:4
  • 页码:719-724
  • DOI:10.1248/bpb.29.719
  • 出版社:The Pharmaceutical Society of Japan
  • 摘要:Thromboxane A2 receptor (TP) consists of two alternatively spliced isoforms, TPα and TPβ, which differ in their cytoplasmic tails. In the present study, we examined the difference in signal transduction of TPα and TPβ, using stably expressing cells of TPα and TPβ. The cells expressing TPα (TPα-SC2) and TPβ (TPβ-SC15) were selected based on the similar binding sites of [3H]-SQ29548, a TP antagonist. U46619, a TP agonist, elicited phosphoinositide hydrolysis in TPα-SC2 and TPβ-SC15 cells with a similar concentration-dependency. U46619 also caused the phosphorylation of extracellular signal-regulated kinase (ERK1/2) in both TPα-SC2 and TPβ-SC15 cells. While the peak of the phosphorylation of ERK1/2 was observed 5 min after addition of U46619 in TPα-SC2 cells, the long lasting phosphorylation up to 60 min was in TPβ-SC15 cells. U46619-induced phosphorylation of ERK1/2 at 5 min was inhibited by pertussis toxin in both cells, suggesting that Gi is involved in the phosphorylation mediated via both TP isoforms. Interfering G12/13 activity by overexpression of p115-RGS reduced U46619-induced ERK1/2 phosphorylation in TPβ-SC15 cells, but not in TPα-SC2 cells. H89, an inhibitor of protein kinase A (PKA), reduced U46619-induced ERK1/2 phosphorylation in TPα-SC2 cells, but not in TPβ-SC15 cells. These results indicate that Gi may be involved in TP-mediated ERK1/2 phosphorylation in both isoforms. In addition, H89-sensitive kinase and G12/13 may be involved in TP-mediated ERK1/2 phosphorylation in TPα and TPβ, respectively.
  • 关键词:thromboxane A2;thromboxane A2 receptor-α (TPα);thromboxane A2 receptor-β (TPβ);extracellular signal-regulated kinase (ERK1/2)
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