The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Expression of the human multidrug resistance cDNA in insect cells generates a high activity drug-stimulated membrane ATPase.
Open accessAbstract
Drug-resistant tumor cells actively extrude a variety of chemotherapeutic agents by the action of the multi-drug resistance (MDR1) gene product, the plasma membrane P-glycoprotein. In this report we show that the expression of the human MDR1 gene in cultured Sf9 insect cells via a baculovirus vector generates a high activity vanadate-sensitive membrane ATPase. This ATPase is markedly stimulated by drugs known to interact with the P-glycoprotein, such as vinblastine and verapamil, and the ability of the various drugs to stimulate the ATPase corresponds to their previously observed affinity for this transporter. The drug-stimulated ATPase is not present in uninfected or mock-infected Sf9 cells, and its appearance correlates with the appearance of the MDR1 gene product detected with a monoclonal anti-MDR protein antibody and by labeling with 8-azido-ATP. The drug-induced ATPase requires magnesium ions, does not utilize ADP or AMP as substrates, exhibits a half-maximal activation at about 0.5 mM MgATP, and its maximal activity (about 3-5 mumol/mg MDR protein/min) approaches that of the well characterized ion transport ATPases. These results provide the first direct demonstration of a high capacity drug-stimulated ATPase activity of the human multidrug resistance protein and offer a new and simple assay for the investigation of functional interactions of various drugs with this clinically important enzyme.
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Cites
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Cited by
Targeting multidrug resistance in cancer
Szakács, G., Paterson, J. K., Ludwig, J. A., Booth-Genthe, C., & Gottesman, M. M. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd1984 · Cited by 3,609
The Sister of P-glycoprotein Represents the Canalicular Bile Salt Export Pump of Mammalian Liver
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The molecular basis of multidrug resistance in cancer: The early years of P‐glycoprotein research
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GENETIC ANALYSIS OF THE MULTIDRUG TRANSPORTER
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Self-citationSun, H., Molday, R. S., & Nathans, J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.12.8269 · Cited by 353
Metadata
- Authors
- Sarkadi, B., Price, E. M., Boucher, R. C., Germann, U. A., & Scarborough, G. A.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1992-03
- Volume
- 267
- Issue
- 7
- Pages
- 4854-4858
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2170734806
- Cited by
- 632
- References
- 30
- FWCI
- 13.43
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Sarkadi, B., Price, E. M., Boucher, R. C., Germann, U. A., & Scarborough, G. A. (1992). Expression of the human multidrug resistance cDNA in insect cells generates a high activity drug-stimulated membrane ATPase. Journal of Biological Chemistry. https://doi.org/10.1016/s0021-9258(18)42909-2
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