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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
13
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pubmed:dateCreated |
1990-6-4
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pubmed:abstractText |
Studies were undertaken to identify the protein kinase(s) responsible for P-glycoprotein phosphorylation in multidrug-resistant (KB-V1) human carcinoma cells and to elucidate the functional role of phosphorylation. P-glycoprotein migrated on sodium dodecyl sulfate gels with apparent Mr 150,000 and is termed P150. When KB-V1 membrane vesicles were incubated with [gamma-32P] ATP, P150 was phosphorylated by an endogenous kinase that exhibited properties of membrane-inserted protein kinase C (PKC). Both membrane-bound P150 and purified P150 served as effective substrates for highly purified rat brain PKC which incorporated approximately 0.6 mol of phosphate/mol of P150. Enzyme assays showed that KB-V1 cells exhibit 4-fold higher PKC activity compared with the drug-sensitive KB-3 cell line. The basal phosphorylation of P150 observed in 32P-labeled cells was increased 2-fold by phorbol ester (PMA) treatment and reduced 30% by treatment with the isoquinolinsulfonamide H-7. Phosphopeptide maps of partially digested P150, phosphorylated either in vitro with PKC or in intact 32P-labeled control or PMA-stimulated cells, were indistinguishable from one another. Drug accumulation assays revealed that PMA treatment of KB-V1 cells significantly reduced [3H]vinblastine accumulation induced by verapamil or by tetrandrine. The results suggest that PKC is primarily responsible for P150 phosphorylation in KB-V1 cells and that phosphorylation may play a modulatory role in the drug transport process.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Alkaloids,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Phytogenic,
http://linkedlifedata.com/resource/pubmed/chemical/Benzylisoquinolines,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/P-Glycoprotein,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphates,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/Verapamil,
http://linkedlifedata.com/resource/pubmed/chemical/Vinblastine,
http://linkedlifedata.com/resource/pubmed/chemical/tetrandrine
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
5
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pubmed:volume |
265
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7679-86
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:1970571-Adenosine Triphosphate,
pubmed-meshheading:1970571-Alkaloids,
pubmed-meshheading:1970571-Antineoplastic Agents, Phytogenic,
pubmed-meshheading:1970571-Benzylisoquinolines,
pubmed-meshheading:1970571-Biological Transport,
pubmed-meshheading:1970571-Cell Membrane,
pubmed-meshheading:1970571-Drug Resistance,
pubmed-meshheading:1970571-Humans,
pubmed-meshheading:1970571-KB Cells,
pubmed-meshheading:1970571-Kinetics,
pubmed-meshheading:1970571-Membrane Glycoproteins,
pubmed-meshheading:1970571-Neoplasm Proteins,
pubmed-meshheading:1970571-P-Glycoprotein,
pubmed-meshheading:1970571-Phosphates,
pubmed-meshheading:1970571-Phosphorylation,
pubmed-meshheading:1970571-Protein Kinase C,
pubmed-meshheading:1970571-Tetradecanoylphorbol Acetate,
pubmed-meshheading:1970571-Verapamil,
pubmed-meshheading:1970571-Vinblastine
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pubmed:year |
1990
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pubmed:articleTitle |
Protein kinase C phosphorylates P-glycoprotein in multidrug resistant human KB carcinoma cells.
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pubmed:affiliation |
Department of Biological Chemistry, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486.
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pubmed:publicationType |
Journal Article
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