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人类尿苷核苷酸受体基因的克隆、表达及染色体定位

Cloning, expression, and chromosomal localization of the human uridine nucleotide receptor gene.

作者信息

Nguyen T, Erb L, Weisman G A, Marchese A, Heng H H, Garrad R C, George S R, Turner J T, O'Dowd B F

机构信息

Addiction Research Foundation, Toronto, Ontario, Canada.

出版信息

J Biol Chem. 1995 Dec 29;270(52):30845-8. doi: 10.1074/jbc.270.52.30845.

Abstract

Extracellular ATP and ADP mediate diverse physiological responses in mammalian cells, in part through the activation of G protein-coupled P2 purinoceptors. The cloning and expression of cDNAs encoding several P2 purinoceptor subtypes have enabled rapid advances in our understanding of the structural and functional properties of these receptors. The current report describes the isolation of a gene from a human genomic library that encodes a protein with the greatest similarity to the human P2U purinoceptor, a subtype that is distinguished by its ability to be activated by uridine nucleotides as well as adenine nucleotides. When expressed in a mammalian cell line, this novel receptor is activated specifically by UTP and UDP but not by ATP and ADP. Activation of this uridine nucleotide receptor resulted in increased inositol phosphate formation and calcium mobilization. Fluorescence in situ hybridization revealed that the gene encoding the uridine nucleotide receptor is located in region q13 of the X chromosome. Dendrogram analysis of the G protein-coupled P2 purinoceptors and the uridine nucleotide receptor indicates that these receptors belong to a family that may be more aptly named nucleotide receptors.

摘要

细胞外ATP和ADP介导哺乳动物细胞中的多种生理反应,部分是通过激活G蛋白偶联的P2嘌呤受体来实现的。编码几种P2嘌呤受体亚型的cDNA的克隆和表达,使我们对这些受体的结构和功能特性的理解取得了迅速进展。本报告描述了从人类基因组文库中分离出一个基因,该基因编码的蛋白质与人类P2U嘌呤受体具有最大的相似性,P2U嘌呤受体是一种亚型,其特点是能够被尿苷核苷酸以及腺嘌呤核苷酸激活。当在哺乳动物细胞系中表达时,这种新型受体特异性地被UTP和UDP激活,而不被ATP和ADP激活。这种尿苷核苷酸受体的激活导致肌醇磷酸形成增加和钙动员。荧光原位杂交显示,编码尿苷核苷酸受体的基因位于X染色体的q13区域。对G蛋白偶联的P2嘌呤受体和尿苷核苷酸受体的系统发育分析表明,这些受体属于一个可能更恰当地称为核苷酸受体的家族。

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