Isolation of a human cDNA that complements a mutant hamster cell defective in methotrexate uptake.
A clone has been isolated from a human lymphoblastic cDNA expression library that complements a mutant Chinese hamster cell defective in the uptake of the folate analogue methotrexate. When transfected with this clone the mutant cells regain the ability to transport the drug and, as a consequence, become sensitive to its cytotoxic action. The clone is 2863 base pairs long and has an open reading frame of 1770 base pairs that codes for a putative protein of 64 kDa. The putative protein has 51 and 50% identity at the amino acid level with the mouse and hamster functions, respectively, involved in the transport of reduced folates. Together these three proteins share 47% identity and have similar predicted structural features. The data are consistent with this human clone encoding either the reduced folate transporter or an auxiliary function that interacts with this transporter.
Department of Microbiology and Immunology, University of Western Ontario, London, Canada.
F M
FM
Williams
W F
WF
Flintoff
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D016466:CHO Cells; D006528:Carcinoma, Hepatocellular; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism*; D006224:Cricetinae; D018076:DNA, Complementary / Q000302:isolation & purification / Q000378:metabolism*; D005260:Female; D058973:Folate Receptors, GPI-Anchored; D005816:Genetic Complementation Test; D006801:Humans; D007700:Kinetics; D008113:Liver Neoplasms; D008727:Methotrexate / Q000378:metabolism* / Q000633:toxicity; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010641:Phenotype; D010957:Plasmids; D011956:Receptors, Cell Surface; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D018076:DNA, Complementary; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D008727:Methotrexate