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Review ArticleMinireview

Protein Kinases and Cross-talk between Post-translational Modifications in the Regulation of Drug Transporters

Xuyang Wang and Mei Hong
Molecular Pharmacology January 2023, 103 (1) 9-20; DOI: https://doi.org/10.1124/molpharm.122.000604
Xuyang Wang
College of Life Sciences, South China Agricultural University, Guangzhou, China (X.W. and M.H.), and Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, South China Agricultural University, Guangzhou, China (M.H.)
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Mei Hong
College of Life Sciences, South China Agricultural University, Guangzhou, China (X.W. and M.H.), and Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, South China Agricultural University, Guangzhou, China (M.H.)
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Abstract

Drug transporters are modulators for drug absorption, distribution, and excretion. Key drug transporters including P-glycoprotein and breast cancer resistance protein of the ABC superfamily; organic anion transporting polypeptide 1B1 and 1B3, organic anion transporter 1 and 3, and organic cation transporter 2, as well as multidrug and toxin extrusion 1 and 2 of the SLC superfamily have been recommended by regulatory agencies to be investigated and evaluated in drug-drug interaction (DDI) studies due to their important roles in determining the efficacy, toxicity and DDI of various drugs. Drug transporters are subjected to multiple levels of control and post-translational modifications (PTMs) provide rapid and versatile ways of regulation. Under pathologic and/or pharmacological conditions, PTMs may be altered in the cellular system, leading to functional changes of transporter proteins. Phosphorylation is by far the most actively investigated form of PTMs in the regulation of transporters. Further, studies in recent years also found that protein kinases coordinate with other PTMs for the dynamic control of these membrane proteins. Here we summarized the regulation of major drug transporters by protein kinases and their cross-talking with other PTMs that may generate a complex regulatory network for fine-tuning the function of these important drug processing modulators.

SIGNIFICANCE STATEMENT Kinases regulate drug transporters in versatile manners; Kinase regulation cross-talks with other PTMs, forming a complex network for transporter regulation; Pathological and/or pharmacological conditions may alter PTMs and affect transporter function with different molecular mechanisms.

Footnotes

    • Received August 5, 2022.
    • Accepted October 3, 2022.
  • This work was supported by Natural Science Foundation of Guangdong Province [grant number 2022A1515010552] and National Natural Science Foundation of China [grant number U1832101 and 81373473] to MH. No author has an actual or perceived conflict of interest with the contents of this article.

  • dx.doi.org/10.1124/molpharm.122.000604.

  • Copyright © 2022 by The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 103 (1)
Molecular Pharmacology
Vol. 103, Issue 1
1 Jan 2023
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Review ArticleMinireview

Wang and Hong

Xuyang Wang and Mei Hong
Molecular Pharmacology January 1, 2023, 103 (1) 9-20; DOI: https://doi.org/10.1124/molpharm.122.000604

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Review ArticleMinireview

Wang and Hong

Xuyang Wang and Mei Hong
Molecular Pharmacology January 1, 2023, 103 (1) 9-20; DOI: https://doi.org/10.1124/molpharm.122.000604
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