Molecular and Cellular Biochemistry

, Volume 461, Issue 1–2, pp 103–118 | Cite as

G protein-coupled receptor kinase 5 modifies cancer cell resistance to paclitaxel

  • Joann Lagman
  • Paula Sayegh
  • Christina S. Lee
  • Sarah M. Sulon
  • Alec Z. Jacinto
  • Vanessa Sok
  • Natalie Peng
  • Deniz Alp
  • Jeffrey L. Benovic
  • Christopher H. SoEmail author


G protein-coupled receptor kinases (GRKs) phosphorylate the activated forms of G protein-coupled receptors (GPCRs), leading to receptor desensitization and internalization. In addition, GRKs can modify the activity of many non-GPCR-signaling pathways as well, controlling other cellular functions beyond that directly associated with a GPCR. In this report, we show that cervical cancer HeLa cells and breast cancer MDA MB 231 cells with reduced GRK5 expression display increased sensitivity to the apoptotic effects of paclitaxel (Taxol). This effect in cancer cells with low GRK5 levels could be because of blunted histone deacetylase 6 (HDAC6) activity that leads to an increase in α-tubulin acetylation levels, which augments paclitaxel sensitivity. We demonstrate that GRK5 and HDAC6 form a signaling complex in cells and in vitro. GRK5 phosphorylates HDAC6 at Ser-21 to promote its deacetylase activity. Therefore, the GRK5–HDAC6 interaction may contribute to paclitaxel resistance in cancer cells.


G protein-coupled receptor kinase Paclitaxel Histone deacetylase Acetylation Cancer 



G protein-coupled receptor kinase


G protein-coupled receptors


Histone deacetylase




Polo-like kinase 1


Compliance with ethical standards

Conflict of interest

Authors declare that there are no competing interests associated with the manuscript.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Joann Lagman
    • 1
  • Paula Sayegh
    • 1
  • Christina S. Lee
    • 1
  • Sarah M. Sulon
    • 2
  • Alec Z. Jacinto
    • 1
  • Vanessa Sok
    • 1
  • Natalie Peng
    • 1
  • Deniz Alp
    • 1
  • Jeffrey L. Benovic
    • 2
  • Christopher H. So
    • 1
    Email author
  1. 1.Roseman University of Health Sciences School of PharmacyHendersonUSA
  2. 2.Department of Biochemistry and Molecular BiologyThomas Jefferson UniversityPhiladelphiaUSA

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