Cloning of a human purinergic P2Y receptor coupled to phospholipase C and adenylyl cyclase

被引:301
作者
Communi, D
Govaerts, C
Parmentier, M
Boeynaems, JM
机构
[1] Free Univ Brussels, Sch Med, Inst Interdisciplinary Res, B-1070 Brussels, Belgium
[2] Free Univ Brussels, Hop Erasme, Dept Med Chem, B-1070 Brussels, Belgium
关键词
D O I
10.1074/jbc.272.51.31969
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
Clones encoding a new human P2Y receptor, provisionally called P2Y(11), have been isolated from human placenta complementary DNA and genomic DNA libraries, The 1113-base pair open reading frame is interrupted by one intron, The P2Y(11) receptor is characterized by considerably larger second and third extracellular loops than the subtypes described so far. The deduced amino acid sequence exhibits 33% amino acid identity with the P2Y(1) receptor, its closest homolog. Northern blot analysis detected human P2Y(11) receptor messenger RNA in spleen and HL-60 cells. The level of P2Y(11) transcripts was strongly increased in these cells after granulocyte differentiation induced by retinoic acid or dimethyl sulfoxide. The new receptor was stably expressed in 1321N1 astrocytoma and CHO-K1 cells, where it couples to the stimulation of both the phosphoinositide and adenylyl cyclase pathways, a unique feature among the P2Y family. The rank order of agonists potency was: ATP > 8-methylthio-ATP >>> ADP, whereas UTP and UDP were inactive, indicating that it behaves as a selective purinoceptor.
引用
收藏
页码:31969 / 31973
页数:5
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