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Phosphorylation of the multidrug resistance associated glycoprotein

Journal Article · · Biochemistry; (United States)
DOI:https://doi.org/10.1021/bi00396a005· OSTI ID:5562562
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Drug-resistant cell lines derived from the mouse macrophage-like cell line J774.2 express the multidrug resistant phenotype which includes the overexpression of a membrane glycoprotein (130-140 kilodaltons). Phosphorylation of this resistant-specific glycoprotein (P-glycoprotein) in intact cells and in cell-free membrane fractions has been studied. The phosphorylated glycoprotein can be immunoprecipitated by a rabbit polyclonal antibody specific for the glycoprotein. Phosphorylation studies done with partially purified membrane fractions derived from colchicine-resistant cells indicated that (a) phosphorylation of the glycoprotein in 1 mM MgCl/sub 2/ was enhanced a minimum of 2-fold by 10 ..mu..M cAMP and (b) the purified catalytic subunit of the cAMP-dependent protein kinase (protein kinase A) phosphorylated partially purified glycoprotein that was not phosphorylated by (..gamma..-/sup 32/P)ATP alone, suggesting that autophosphorylation was not involved. These results indicate that the glycoprotein is a phosphoprotein and that at least one of the kinases responsible for its phosphorylation is a membrane-associated protein kinase A. The state of phosphorylation of the glycoprotein, which is a major component of the multidrug resistance phenotype, may be related to the role of the glycoprotein in maintaining drug resistance.
Research Organization:
Albert Einstein College of Medicine, Bronx, NY
OSTI ID:
5562562
Journal Information:
Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 26:22; ISSN BICHA
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMALS
ATP
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CARBOHYDRATES
CELL CONSTITUENTS
CELL MEMBRANES
CHEMICAL REACTIONS
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
ELECTROPHORESIS
GLUCOPROTEINS
ISOTOPES
LABELLING
LIGHT NUCLEI
MACROPHAGES
MAMMALS
MEMBRANES
MICE
NUCLEI
NUCLEOTIDES
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PHAGOCYTES
PHENOTYPE
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PHOSPHORYLATION
PROTEINS
RADIOISOTOPES
RODENTS
SACCHARIDES
SOMATIC CELLS
VERTEBRATES