P-glycoprotein gene (MDR1) cDNA from human adrenal: normal P-glycoprotein carries Gly185 with an altered pattern of multidrug resistance.
We isolated a full-length MDR1 cDNA from human adrenal where P-glycoprotein is expressed at high level. The deduced amino acid sequence shows two amino acid differences from the sequence of P-glycoprotein obtained from colchicine-selected multidrug resistant cultured cells. The amino acid substitution Gly----Val at codon 185 in P-glycoprotein from colchicine resistant cells occurred during selection of cells in colchicine. As previously reported, cells transfected with the MDR1 cDNA carrying Val185 acquire increased resistance to colchicine compared to other drugs. The other amino acid substitution Ser----Ala at codon 893 probably reflects genetic polymorphism. The MDR1 gene, the major member of the P-glycoprotein gene family expressed in human adrenal, is sufficient to confer multidrug-resistance on culture cells.
Kioka
N
N
Department of Agricultural Chemistry, Kyoto University, Japan.
Tsubota
J
J
Kakehi
Y
Y
Komano
T
T
Gottesman
M M
MM
Pastan
I
I
Ueda
K
K
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000311:Adrenal Glands / Q000032:analysis* / Q000502:physiology; D000409:Alanine / Q000235:genetics; D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA / Q000302:isolation & purification*; D004351:Drug Resistance; D005822:Genetic Vectors; D005998:Glycine / Q000235:genetics*; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D012694:Serine / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000032:analysis / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008562:Membrane Glycoproteins; D012694:Serine; D004247:DNA; D000409:Alanine; D005998:Glycine