PHOSPHORYLATION OF THE MR170,000 TO 180,000 GLYCOPROTEIN SPECIFIC TO MULTIDRUG-RESISTANT TUMOR-CELLS - EFFECTS OF VERAPAMIL, TRIFLUOPERAZINE, AND PHORBOL ESTERS

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  • 1 June 1987
    • journal article
    • research article
    • Vol. 47  (11) , 2860-2865
Abstract
An overexpression of plasma membrane glycoprotein with a relative molecular mass (Mr) of 170,000-180,000 is consistently found in different multidrug-resistant human and animal cell lines, although the functional role of the protein in multidrug resistance is not fully understood. It has been reported previously that the Mr 170,000-180,000 glycoprotein is involved, directly or indirectly, in the drug transport mechanism and the proliferation of multidrug-resistant tumor cells. In an attempt to clarify further the function of the Mr 170,000-180,000 glycoprotein, we have studied the phosphorylation state of the protein in intact K562/ADM cells and found that: (1) the protein is phosphorylated in the basal state; (b) verapamil and trifluoperazine, which inhibit the active drug efflux and restore drug sensitivity in resistant cells, caused an increase in the phosphorylation of the Mr 170,000-180,000 glycoprotein; (c) 4.beta.-phorbol-12.beta.-myristate-13.alpha.-acetate and 1-oleoyl 2-acetylglycerol enhanced phosphorylation of the protein; (d) the protein was phosphorylated at serine residues; (e) tryptic phosphopeptide mapping of the Mr 170,000-180,000 glycoprotein showed that 4.beta.-phorbol-12.beta.-myristate-13.alpha.-acetate treatment induced an increase in phosphorylation at different sites of the protein from those induced by verapamil or trifluoperazine treatment, suggesting that the protein is phosphorylated by an aray of complex regulation mechanisms. Phosphorylation of the Mr 170,000-180,000 glycoprotein might play a role in the regulation of processes affecting cellular function in multidrug resistance.