Biosynthesis of heterogeneous forms of multidrug resistance-associated glycoproteins.
Multidrug-resistant J774.2 mouse macrophage-like cells, selected for resistance to colchicine, vinblastine, or taxol, overexpress antigenically related glycoproteins with distinct electrophoretic mobilities. These plasma membrane glycoproteins are likely to play a pivotal role in the expression of the multidrug resistance phenotype. To determine how these multidrug resistance-associated glycoproteins differ, the biosynthesis and N-linked carbohydrate composition of these proteins were examined and compared. Vinblastineor colchicine-selected cells made a 125-kDa precursor that was rapidly processed (t1/2 approximately equal to 20 min) to mature forms of 135 and 140 kDa, respectively. Heterogeneity between the 135- and 140-kDa forms of the molecule can be attributed to N-linked carbohydrate. In contrast, taxol-selected cells made two precursors, 125 and 120 kDa, which appeared within 5 and 15 min after the onset of pulse labeling, respectively. They were processed to mature forms of 140 and 130 kDa. Since a single deglycosylated precursor or mature form was not observed after enzymatic removal of N-linked oligosaccharides, other differences, besides N-linked glycosylation, which occur in early processing compartments, are likely to account for the two multidrug resistance-associated glycoproteins in taxol-selected cells. These results demonstrate that a family of multidrug resistance-associated glycoproteins can be differentially expressed.
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D003078:Colchicine / Q000494:pharmacology; D004351:Drug Resistance; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000302:isolation & purification; D051379:Mice; D009844:Oligosaccharides / Q000032:analysis; D017239:Paclitaxel; D014747:Vinblastine / Q000494:pharmacology
D000470:Alkaloids; D008565:Membrane Proteins; D009844:Oligosaccharides; D014747:Vinblastine; D017239:Paclitaxel; D003078:Colchicine