FUNCTIONALLY ACTIVE HOMODIMER OF P-GLYCOPROTEIN IN MULTIDRUG-RESISTANT TUMOR-CELLS

P-glycoprotein plays a key role in multidrug resistance of tumor cells. In order to elucidate the possible quarternary structure/function relationship of P-glycoprotein, we treated multidrug-resistant human leukemia K562/ADM cells with the crosslinking reagent, disuccinimidyl suberate. In addition to 180K P-glycoprotein, a 340K protein was immunoprecipitated with an anti-P-glycoprotein monoclonal antibody, MRK-16. The 340K protein is most probably a dimeric P-glycoprotein, since only the 180K P-glycoprotein was immunoprecipitated with MRK-16 when K562/ADM ceils were treated with the cleavable crosslinking reagent, dithiobis(succinimidylpropionate), and analysed under reduced conditions. The dimeric P-glycoprotein was photolabeled with [3H]azidopine like the 180K monomeric P-glycoprotein and the photolabeling was inhibited by excess amount of vincristine and verapamil. The dimeric P-glycoprotein could be a functionally active form of the protein involved in the transport of antitumor agents. © 1992 Academic Press, Inc.