The inducible G protein-coupled receptor edg-1 signals via the G(i)/nitrogen-activated protein kinase pathway

被引:151
作者
Lee, MJ [1 ]
Evans, M [1 ]
Hla, T [1 ]
机构
[1] AMER RED CROSS, JEROME H HOLLAND LAB, DEPT BIOL MOLEC, ROCKVILLE, MD 20855 USA
关键词
D O I
10.1074/jbc.271.19.11272
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The edg-1 gene encodes an inducible G protein-coupled receptor (GPR) homologue that is induced during the in vitro differentiation of human endothelial cells. The aim of this study was to investigate the G protein-coupling and -signaling properties of the edg-1 polypeptide. The third cytosolic loop (i(3)) of edg-1 associates with G(i alpha) and G(o alpha) polypeptides in a guanosine 5'-O-(thiotriphosphate)-sensitive manner. Immunoprecipitation of the edg-1 polypeptide in transfected cells results in the co-precipitation of G(i alpha 1) and G(i alpha 3) polypeptides. These data strongly suggest that edg-1 is capable of coupling to the G(i) pathway. Overexpression of the edg-1 GPR in human embryonic kidney 293 cells results in the sustained activation of the MAP kinase activity that is blocked by pertussis toxin treatment. Moreover, NIH3T3 cells permanently transfected with edg-1 exhibit enhanced MAP kinase and phospholipase A(2) activities. These data suggest that the G(i)/mitogen-activated protein kinase pathway is a major signaling pathway regulated by the orphan receptor edg-1.
引用
收藏
页码:11272 / 11279
页数:8
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