Selective Loss of Sphingosine 1-Phosphate Signaling with No Obvious Phenotypic Abnormality in Mice Lacking Its G Protein-coupled Receptor, LP B3/EDG-3

Isao Ishii, Beth Friedman, Xiaoqin Ye, Shuji Kawamura, Christine McGiffert, James J.A. Contos, Marcy A. Kingsbury, Guangfa Zhang, Joan Heller Brown, Jerold Chun

研究成果: Article査読

237 被引用数 (Scopus)

抄録

Sphingosine 1-phosphate (S1P) exerts diverse physiological actions by activating its cognate G protein-coupled receptors. Five S1P receptors have been identified in mammals: LPB1/EDG-1, LP B2/H218/AGR16/EDG-5, LPB3/EDG-3, LP B4/NRG-1/EDG-8, and LPC1/EDG-6. One of these receptors, LPB1, has recently been shown to be essential for mouse embryonic development. Here we disrupted the lPB3 gene in mice, resulting in the complete absence of lPB3 gene, transcript, and LPB3 protein. LPB3-null mice were viable and fertile and developed normally with no obvious phenotypic abnormality. We prepared mouse embryonic fibroblast (MEF) cells to examine effects of LPB3 deletion on S1P-induced signal transduction pathways. Wild-type MEF cells expressed lP B1, lPB2, and lPB3 but neither lPB4 nor lPC1, and they were highly responsive to S1P in phospholipase C (PLC) activation, adenylyl cyclase inhibition, and Rho activation. Identically prepared LPB3-null MEF cells showed significant decreases in PLC activation, slight decreases in adenylyl cyclase inhibition, and no change in Rho activation. Retrovirus-mediated rescue of the LPB3 receptor in LPB3-null MEF cells restored S1P-dependent PLC activation and adenylyl cyclase inhibition. These results indicate a nonessential role for LPB3 in normal development of mouse but show nonredundant cellular signaling mediated by a single type of S1P receptor.

本文言語English
ページ(範囲)33697-33704
ページ数8
ジャーナルJournal of Biological Chemistry
276
36
DOI
出版ステータスPublished - 2001 9月 7

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学

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