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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
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Protein kinase C phosphorylates P-glycoprotein in multidrug resistant human KB carcinoma cells

T C Chambers1, E M McAvoy, J W Jacobs

  • 1Department of Biological Chemistry, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486.

The Journal of Biological Chemistry
|May 5, 1990
PubMed

Insights

Protein kinase C (PKC) phosphorylates P-glycoprotein (P150) in multidrug-resistant cells. This phosphorylation by PKC may modulate the drug transport process, impacting chemotherapy efficacy.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Multidrug resistance (MDR) in cancer is a significant clinical challenge.
  • P-glycoprotein (P150) is a key efflux pump involved in MDR.
  • The role of P150 phosphorylation in MDR is not fully understood.

Purpose of the Study:

  • Identify the kinase responsible for P150 phosphorylation in MDR cells.
  • Determine the functional significance of P150 phosphorylation in drug transport.

Main Methods:

  • In vitro kinase assays using [gamma-32P] ATP.
  • Enzyme activity assays for protein kinase C (PKC).
  • Phosphopeptide mapping and drug accumulation studies.

Main Results:

  • An endogenous kinase with properties of PKC phosphorylates P150.
  • KB-V1 cells show higher PKC activity than drug-sensitive cells.
  • PKC activation reduces [3H]vinblastine accumulation in KB-V1 cells.

Conclusions:

  • Protein kinase C (PKC) is the primary kinase phosphorylating P150 in multidrug-resistant cells.
  • P150 phosphorylation by PKC may play a modulatory role in P-glycoprotein drug transport function.

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