P-GLYCOPROTEIN GENES IN THE WINTER FLOUNDER, PLEURONECTES-AMERICANUS - ISOLATION OF 2 TYPES OF GENOMIC CLONES CARRYING 3' TERMINAL EXONS

被引:40
作者
CHAN, KM
DAVIES, PL
CHILDS, S
VEINOT, L
LING, V
机构
[1] QUEENS UNIV,DEPT BIOCHEM,KINGSTON K7L 3N6,ONTARIO,CANADA
[2] UNIV TORONTO,ONTARIO CANC INST,TORONTO M5S 1A1,ONTARIO,CANADA
[3] UNIV TORONTO,DEPT MED BIOPHYS,TORONTO M5S 1A1,ONTARIO,CANADA
关键词
ATP-BINDING SITE; MULTIDRUG RESISTANCE; P-GLYCOPROTEIN; 3' UNTRANSLATED REGION; DETOXIFICATION; (WINTER FLOUNDER);
D O I
10.1016/0167-4781(92)90140-U
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
In mammals, P-glycoprotein (P-gp) is encoded by two or more highly conserved genes that differ in their abilities to transport drugs. One isoform class (class I) is consistantly associated with the multidrug resistance phenotype, while the other (class III) is not. This study was designed to enumerate the P-gp genes in fish and determine how they are related to the two functional classes already defined in mammals. Southern blot analysis using a conserved single exon from the 3' terminal region of hamster P-gp cDNA (pEX1-172) as a probe indicated that there were two P-gp genes in righteye flounders. Subsequently, two sets of clones were isolated from a winter flounder genomic library that correspond to the 3' ends of the two flounder P-gp genes. Sequence analysis was done on two key areas: the 3' ATP binding site and the 3' terminal exon, both of which were found to be homologous with their mammalian counterparts. Despite high levels of sequence identity in the predicted coding regions of the gene fragments it has not been possible to use these sequences to relate the homologs to particular mammalian classes of P-gp genes, perhaps because of gene conversion between mammalian P-gp gene-s. These cloned sequences are the first set of P-gp genes reported in lower vertebrates and will be useful for delineating the expression of P-gp genes in fish and understanding the role of P-gp in fish physiology.
引用
收藏
页码:65 / 72
页数:8
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