Vinblastine photoaffinity labeling of a high molecular weight surface membrane glycoprotein specific for multidrug-resistant cells.
Photoactive radioactive analogues of vinblastine were used to photoaffinity label membranes of Chinese hamster lung drug-sensitive (DC-3F), multidrug-resistant sublines selected for resistance to vincristine (DC-3F/VCRd-5L) or actinomycin D (DC-3F/ADX), and revertant (DC-3F/ADX-U) cells. A radiolabeled doublet (150-180 kDa) consisting of a major and minor band which was barely detectable in parental drug-sensitive cells was increased up to 150-fold in the drug-resistant variants but only 15-fold in the revertant cells. Photoaffinity labeling in the presence of 200-fold excess vinblastine reduced radiolabeling of the 150-180-kDa species up to 96%, confirming its Vinca alkaloid binding specificity. The radiolabeled doublet comigrated with a Coomassie Blue stained polypeptide doublet in the drug-resistant cells and was immunoprecipitated with polyclonal antibody which is specific for the 150-180-kDa surface membrane glycoprotein in multidrug-resistant cell lines. The identification of this Vinca alkaloid acceptor in multidrug-resistant plasma cell membranes suggests the possibility of a direct functional role for the 150-180-kDa surface membrane protein in the development of multidrug resistance.
Safa
A R
AR
Glover
C J
CJ
Meyers
M B
MB
Biedler
J L
JL
Felsted
R L
RL
D000345:Affinity Labels / Q000378:metabolism*; D000818:Animals; D000906:Antibodies; D001386:Azides / Q000378:metabolism; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D003609:Dactinomycin / Q000494:pharmacology; D004351:Drug Resistance; D004591:Electrophoresis, Polyacrylamide Gel; D005470:Fluorometry; D008168:Lung / Q000187:drug effects; D010777:Photochemistry; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000378:metabolism; D014751:Vindesine / Q000031:analogs & derivatives / Q000378:metabolism
D000345:Affinity Labels; D000906:Antibodies; D001386:Azides; C048695:N-(4-azido-3-iodosalicyl)-N'-beta-aminoethylvindesine; C048694:N-(4-azidobenzoyl)-N'-beta-aminoethylvindesine; D003609:Dactinomycin; D014747:Vinblastine; D014751:Vindesine