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Title: Protein kinase Cgamma mediates regulation of proliferation by the serotonin 5-HT2B receptor
Authors: Wouters, Mira
Roeder, Jaime L
Tharayil, Vivek S
Stanich, Jennifer E
Strege, Peter R
Lei, Sha
Bardsley, Michael R
Ordog, Tamas
Gibbons, Simon J
Farrugia, Gianrico # ×
Issue Date: Aug-2009
Series Title: Journal of Biological Chemistry vol:284 issue:32 pages:21177-21184
Abstract: Activation of the 5-hydroxytryptamine receptor 2B (5-HT(2B)), a Gq/11 protein-coupled receptor, results in proliferation of various cell types. The 5-HT(2B) 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-HT(2B) receptor. All experiments were performed on mouse small intestine primary cell cultures. Activation of the 5-HT(2B) receptor by its agonist BW723C86 induced proliferation of ICC. Inhibition of phosphatidylinositol-3'-kinase (PI3'-K) by LY294002 decreased baseline proliferation but had no effect on 5-HT(2B) receptor mediated proliferation. Proliferation of ICC through the 5-HT(2B) receptor was inhibited by the phospholipase C (PLC) inhibitor U73122 and by the inositol 1,4,5-trisphosphate receptor inhibitor Xestospongin C. Calphostin C, the alpha, beta, gamma, mu PKC inhibitor Go6976 and the alpha, beta, gamma, delta, zeta PKC inhibitor Go6983, inhibited 5-HT(2B) receptor mediated proliferation indicating the involvement of PKC alpha, beta or gamma. Of all the PKC isoforms blocked by Go6976, PKCgamma and mu mRNAs were found by single cell PCR to be expressed in ICC. 5-HT(2B) receptor activation in primary cell cultures obtained from PKCgamma (-)/(-) mice did not result in a proliferative response further indicating the requirement for PKCgamma in the proliferative response to 5-HT(2B) receptor activation. The data demonstrate that the 5-HT(2B) receptor induced proliferative response of ICC is through PLC, [Ca2+]i and PKCgamma, implicating this PKC isoform in the regulation of cellular proliferation.
URI: 
ISSN: 0021-9258
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Translational Research in GastroIntestinal Disorders
× corresponding author
# (joint) last author

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