Vinblastine photoaffinity labeling of a high molecular weight surface membrane glycoprotein specific for multidrug-resistant cells

Ahmad Safa, C. J. Glover, M. B. Meyers, J. L. Biedler, R. L. Felsted

Research output: Contribution to journalArticle

240 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6137-6140
Number of pages4
JournalJournal of Biological Chemistry
Volume261
Issue number14
StatePublished - 1986
Externally publishedYes

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Vinblastine
Membrane Glycoproteins
Labeling
Molecular Weight
Molecular weight
Vinca Alkaloids
Cell membranes
Pharmaceutical Preparations
Membrane Proteins
Photoaffinity Labels
Cell Membrane
Multiple Drug Resistance
Dactinomycin
Vincristine
Cricetulus
Plasma Cells
Cells
Membranes
Cell Line
Lung

ASJC Scopus subject areas

  • Biochemistry

Cite this

Vinblastine photoaffinity labeling of a high molecular weight surface membrane glycoprotein specific for multidrug-resistant cells. / Safa, Ahmad; Glover, C. J.; Meyers, M. B.; Biedler, J. L.; Felsted, R. L.

In: Journal of Biological Chemistry, Vol. 261, No. 14, 1986, p. 6137-6140.

Research output: Contribution to journalArticle

Safa, Ahmad ; Glover, C. J. ; Meyers, M. B. ; Biedler, J. L. ; Felsted, R. L. / Vinblastine photoaffinity labeling of a high molecular weight surface membrane glycoprotein specific for multidrug-resistant cells. In: Journal of Biological Chemistry. 1986 ; Vol. 261, No. 14. pp. 6137-6140.
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