Overexpression of a 123-kDa anion transport inhibitor binding protein and two cytoskeleton proteins in Drosophila Kc cell variants resistant to disulfonic stilbenes.
Drugs of the disulfonic stilbene class, which inhibit anion transport in the cell membrane in many cell types, have been found to inhibit anion transport and cell growth in Drosophila Kc cells. Cell variants selected by a stepwise selection protocol for the ability to grow in the presence of the disulfonic stilbenes are severalfold resistant to growth inhibition by the drugs. Both the resistant populations and a cloned cell line show dramatic overexpression of three polypeptides. The most highly overproduced protein is a 123-kDa plasma membrane protein which binds the reversible anion transport inhibitor, flufenamic acid, in a protection biotinylation experiment. The 123-kDa putative anion transport protein copurifies with, and immunologically cross-reacts with, two detergent-insoluble cytoskeleton proteins of 46- and 62-kDa molecular weight, which are each overexpressed more than 8-fold in the variants. Resistance to growth inhibition by the disulfonic stilbenes and amplified expression of the 123-, 62-, and 46-kDa proteins are simultaneously lost over a period of 30 weeks in the absence of selective conditions, suggesting that the function of the overproduced polypeptides is related to growth control in Drosophila cells.
Sherwood
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AC
Department of Pharmacology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway 08854.
John-Alder
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Biessmann
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Sanders
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D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D027321:Anion Transport Proteins; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000096:biosynthesis*; D004261:DNA Replication / Q000187:drug effects; D004330:Drosophila / Q000378:metabolism*; D004351:Drug Resistance; D004591:Electrophoresis, Polyacrylamide Gel; D006358:Hot Temperature; D013267:Stilbenes / Q000494:pharmacology*
D027321:Anion Transport Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D013267:Stilbenes; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid