Protein kinase Cγ mediates regulation of proliferation by the serotonin 5-hydroxytrptamine receptor 2B

Mira M. Wouters, Jaime L. Roeder, Vivek S. Tharayil, Jennifer E. Stanich, Peter R. Strege, Sha Lei, Michael R. Bardsley, Tamas Ordog, Simon J. Gibbons, Gianrico Farrugia

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Activation of the 5-hydroxytryptamine receptor 2B (5-HT2B), a Gq/ 11 protein-coupled receptor, results in proliferation of various cell types. The 5-HT2B receptor is also expressed on the pacemaker cells of the gastrointestinal tract, the interstitial cells of Cajal (ICC), where activation triggers ICC proliferation, The goal of this study was to characterize the mitogenic signal transduction cascade activated by the 5-HT2B receptor. All of the experiments were performed on mouse small intestine primary cell cultures. Activation of the 5-HT2B receptor by its agonist BW723C86 induced proliferation of ICC. Inhibition of phosphatidylinositol 3-kinase by LY294002 decreased base-line proliferation but had no effect on 5-HT2B receptor-mediated proliferation. Proliferation of ICC through the 5-HT2B receptor was inhibited by the phospholipase C inhibitor U73122 and by the inositol 1,4,5-trisphosphate receptor inhibitor Xestospongin C. Calphostin C, the α, β, γ, and μ protein kinase C (PKC) inhibitor Gö6976, and the α, β, γ, δ, and ζ PKC inhibitor Gö6983 inhibited 5-HT2B receptor-mediated proliferation, indicating the involvement of PKC α, β, or γ. Of all the PKC isoforms blocked by Gö6976, PKCγ and μ mRNAs were found by single-cell PCR to be expressed in ICC. 5-HT2B receptor activation in primary cell cultures obtained from PKCγ-/- mice did not result in a proliferative response, further indicating the requirement for PKCγ in the proliferative response to 5-HT2B receptor activation. The data demonstrate that the 5-HT2B receptor-induced proliferative response of ICC is through phospholipase C, [Ca2+]j, and PKCγ, implicating this PKC isoform in the regulation of cellular proliferation.

Original languageEnglish (US)
Pages (from-to)21177-21184
Number of pages8
JournalJournal of Biological Chemistry
Volume284
Issue number32
DOIs
StatePublished - Aug 7 2009

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Protein kinase Cγ mediates regulation of proliferation by the serotonin 5-hydroxytrptamine receptor 2B'. Together they form a unique fingerprint.

  • Cite this

    Wouters, M. M., Roeder, J. L., Tharayil, V. S., Stanich, J. E., Strege, P. R., Lei, S., Bardsley, M. R., Ordog, T., Gibbons, S. J., & Farrugia, G. (2009). Protein kinase Cγ mediates regulation of proliferation by the serotonin 5-hydroxytrptamine receptor 2B. Journal of Biological Chemistry, 284(32), 21177-21184. https://doi.org/10.1074/jbc.M109.015859