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Y(+)型阳离子氨基酸转运:mCAT基因的表达与调控

y(+)-type cationic amino acid transport: expression and regulation of the mCAT genes.

作者信息

MacLeod C L, Finley K D, Kakuda D K

机构信息

Department of Medicine, University of California, San Diego, La Jolla 92093-0961.

出版信息

J Exp Biol. 1994 Nov;196:109-21. doi: 10.1242/jeb.196.1.109.

Abstract

The transport of cationic amino acids across animal cell membranes is largely mediated by a small group of well-described transport system (y+, bo,+, Bo,+). Only recently have genes encoding transport proteins in some of these systems been isolated. Two genes, mCAT-1 and mCAT-2, encode related multiple membrane-spanning proteins that share substantial amino acid sequence identity and virtually superimposable hydrophilicity profiles. mCAT-1 and mCAT-2 proteins expressed in Xenopus oocytes are functionally indistinguishable and similar to transport system y+, but have distinct tissue distribution patterns. mCAT-1 expression is nearly ubiquitous and produces a single protein, while mCAT-2 is highly tissue-specific, has two distinct protein isoforms encoded by a single gene and is expressed in different tissues using at least two widely separated promoters. All three proteins facilitate the ion-independent transport of arginine, lysine and ornithine. Both mCAT-1 and mCAT-2 proteins have low amino acid sequence similarity but strikingly similar hydrophilicity profiles with amino acid antiporters, uniporters and symporters of yeast, fungi and eubacteria. Current work will elucidate whether any of the mCAT proteins interact with members of a newly identified family of single membrane-spanning proteins, such as rBAT, 4F2 and NAA-Tr, which are thought to modulate or activate y+L and/or bo,+ transport systems.

摘要

阳离子氨基酸跨动物细胞膜的转运很大程度上由一小群已被充分描述的转运系统(y+、bo,+、Bo,+)介导。直到最近,这些系统中一些编码转运蛋白的基因才被分离出来。两个基因,即mCAT-1和mCAT-2,编码相关的多次跨膜蛋白,它们具有大量的氨基酸序列同一性以及几乎重叠的亲水性图谱。在非洲爪蟾卵母细胞中表达的mCAT-1和mCAT-2蛋白在功能上无法区分,且与转运系统y+相似,但具有不同的组织分布模式。mCAT-1的表达几乎无处不在,产生单一蛋白,而mCAT-2具有高度的组织特异性,由单个基因编码产生两种不同的蛋白异构体,并使用至少两个相距很远的启动子在不同组织中表达。所有这三种蛋白都促进精氨酸、赖氨酸和鸟氨酸的非离子依赖性转运。mCAT-1和mCAT-2蛋白的氨基酸序列相似性都很低,但与酵母、真菌和真细菌的氨基酸反向转运体、单向转运体和同向转运体具有惊人相似的亲水性图谱。目前的研究工作将阐明mCAT蛋白是否与新发现的单跨膜蛋白家族成员相互作用,例如rBAT、4F2和NAA-Tr,这些蛋白被认为可调节或激活y+L和/或bo,+转运系统。

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