| Autor: |
Rumsby MG; Department of Biology, University of York, York, YO1 5YW, England., mgr1@york.ac.uk., Drew L, Warr JR |
| Jazyk: |
angličtina |
| Zdroj: |
Cytotechnology [Cytotechnology] 1998 Sep; Vol. 27 (1-3), pp. 203-24. |
| DOI: |
10.1023/A:1008073006495 |
| Abstrakt: |
The role of protein kinases in the multidrug resistance phenotype of cancer cell lines is discussed with an emphasis on protein kinase C and protein kinase A. Evidence that P-glycoprotein is phosphorylated by these kinases is summarised and the relationship between P-glycoprotein phosphorylation and the multidrug-resistant phenotype discussed. Results showing that protein kinase C, particularly the alpha subspecies, is overexpressed in many MDR cell lines are described: this common but by no means universal finding seems to be drug- and cell line-dependent and in only in a few cases is there a direct correlation between protein kinase C activity and multidrug resistance. From co-immunoprecipitation results it is suggested that P-glycoprotein is a specific protein kinase C receptor, as well as being a substrate. Revertant experiments provide conflicting results as to a direct relationship between expression of P-glycoprotein and protein kinase C. Evidence that protein kinase A influences P-glycoprotein expression at the gene level is well documented and the mechanisms by which this occurs are becoming clarified. Results on the relationship between protein kinase C and multidrug resistance using many inhibitors and phorbol esters are difficult to interpret because such compounds bind to P-glycoprotein. In spite of huge effort, a direct involvement of protein kinase C in regulating multidrug resistance has not yet been firmly established. However, evidence that PKC regulates a Pgp-independent mechanism of drug resistance is accumulating. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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