Human leukemia and normal leukocytes contain a species of immunoreactive but nonfunctional dihydrofolate reductase

S. P. Rothenberg, M. P. Iqbal

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

A quantitative radioimmunoassay has been developed for human dihydrofolate reductase (tetrahydrofolate dehydrogenase; 5,6,7,8-tetrahydrofolate:NADPH+ oxidoreductase, EC 1.5.1.3) by using antiserum raised in rabbits against the active enzyme purified from calf liver. An immunoreactive protein could be identified in the cytoplasm of chronic myelogenous leukemia cells, which contained no functional dihydrofolate reductase activity. Its concentration was stoichiometric to the volume of cytoplasm assayed and paralleled the standard curve obtained with purified enzyme, indicating that this protein in the human cells is antigenically similar to the homologous antigen. The concentration of this immunoreactive protein in the cytoplasm of human leukemia and normal leukocytes in all instances greatly exceeded the concentration of functional dihydrofolate reductase, which was measured by the binding of [3H]methotrexate. This nonfunctional immunoreactive protein in the cytoplasm and cytosol from two different samples of chronic myelogenous leukemia cells analyzed by gel filtration had an apparent molecular weight of 41,000, which is twice the molecular weight of the functional enzyme.

Original languageEnglish
Pages (from-to)645-649
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume79
Issue number2 I
DOIs
Publication statusPublished - 1982
Externally publishedYes

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