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 l ibrary that complements a mutant Chinese hamster cell defective in the uptake of the folate analogue methotrexate. When transfected with thi s 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 pa irs 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 ham ster functions, respectively, involved in the transport of reduced fol ates. Together these three proteins share 47% identity and have simila r predicted structural features. The data are consistent with this hum an clone encoding either the reduced folate transporter or an auxiliar y function that interacts with this transporter.