Isolation of a hamster cDNA clone coding for a function involved in methotrexate uptake.

F M Williams; R C Murray; T M Underhill; W F Flintoff

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PubMed · 8119923

Isolation of a hamster cDNA clone coding for a function involved in methotrexate uptake.

F M Williams·R C Murray·T M Underhill·W F Flintoff

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Abstract

A clone has been isolated from a Chinese hamster ovary cell cDNA expression library that complements mutant cells defective in the uptake of the folate analogue methotrexate. When transfected with this clone, the mutant cells regain the ability to bind and transport the drug and, as a consequence, become sensitive to its cytotoxic action. The clone is 2314 base pairs long and has an open reading frame of 1557 base pairs that codes for a putative protein of 58 kDa. This novel putative protein has a high content of hydrophobic residues and has a large part of its predicted secondary structure in the form of beta-sheets. In the wild-type cell line and in one of the mutant cell lines, this clone detects an mRNA of 2.5 kilobases, while in another mutant cell line, this message is absent. The data are consistent with this clone encoding either the reduced folate transporter or an auxiliary function that interacts with this transporter. This is the first report of a cDNA coding for a function, other than folate-binding protein, that is involved in the transport of methotrexate.

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ATP Binding Cassette Transporter, Subfamily G, Member 2 ATP-Binding Cassette Transporters Amino Acid Sequence Animals Base Sequence Biological Transport Blotting, Northern CHO Cells Carrier Proteins Cricetinae DNA, Complementary Methotrexate Molecular Sequence Data Mutation Neoplasm Proteins Phenotype Journal Article Research Support, Non-U.S. Gov't

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F M Williams, R C Murray, T M Underhill, W F Flintoff. 1994-02-25. Isolation of a hamster cDNA clone coding for a function involved in methotrexate uptake.. https://pubmed.ncbi.nlm.nih.gov/8119923/

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