Abstract：
:Structural changes in the macromolecular targets of pharmacological agents can result in alterations in the efficacy of these agents. In previous studies, we identified a variant structural form of thymidylate synthase (TS) that is associated with relative resistance to 5-fluoro-2'-deoxyuridine, in a human colonic tumor cell line. We now report on the use of DNA transfer techniques to examine directly the effects of each TS form on drug response. TS cDNA constructs, corresponding to the normal or variant TS mRNA, were expressed in Chinese hamster lung cells or in Escherichia coli, and response to 5-fluoro-2'-deoxyuridine was determined. We observed that expression of the variant TS, which differs from the normal form by a tyrosine to histidine substitution at residue 33, confers a 4-fold level of drug resistance in the mammalian cells, as well as in bacteria. The possible role of Tyr-33 in 5-fluoropyrimidine-mediated inhibition of TS is discussed.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Barbour KW,Hoganson DK,Berger SH,Berger FGkeywords:
subject
Has Abstractpub_date
1992-08-01 00:00:00pages
242-8issue
2eissn
0026-895Xissn
1521-0111journal_volume
42pub_type
杂志文章abstract：:Neuroactive steroids are efficacious potentiators of GABA-A receptors. Recent work has identified a site in the alpha1 subunit of the GABA-A receptor, that is essential for potentiation by steroids. However, each receptor contains two copies of the alpha1 subunit. We generated concatemers of subunits so that the alpha...
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journal_title：Molecular pharmacology
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更新日期：1992-01-01 00:00:00
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journal_title：Molecular pharmacology
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更新日期：1986-06-01 00:00:00
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journal_title：Molecular pharmacology
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更新日期：1994-10-01 00:00:00
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journal_title：Molecular pharmacology
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更新日期：1992-11-01 00:00:00
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journal_title：Molecular pharmacology
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doi：
更新日期：1994-09-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-03-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-12-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.53.3.446
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1986-12-01 00:00:00
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journal_title：Molecular pharmacology
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doi：
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journal_title：Molecular pharmacology
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doi：
更新日期：1994-08-01 00:00:00
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journal_title：Molecular pharmacology
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journal_title：Molecular pharmacology
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doi：
更新日期：1983-03-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-02-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-11-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-04-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-11-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.61.2.446
更新日期：2002-02-01 00:00:00
