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Updated: Jan 20, 2026

Characterization at the Molecular Level using Robust Biochemical Approaches of a New Kinase Protein
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Characterization at the Molecular Level using Robust Biochemical Approaches of a New Kinase Protein

Published on: June 30, 2019

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Protein kinase C{gamma} mediates regulation of proliferation by the serotonin 5-hydroxytryptamine receptor 2B

Mira M Wouters1, Jaime L Roeder, Vivek S Tharayil

  • 1Enteric Neuroscience Program, Division of Gastroenterology and Hepatology, Miles and Shirley Fiterman Center for Digestive Diseases, Rochester, Minnesota 55905, USA.

The Journal of Biological Chemistry
|June 18, 2009
PubMed

Insights

Activation of the 5-hydroxytryptamine receptor 2B (5-HT2B) triggers interstitial cells of Cajal (ICC) proliferation. This study shows 5-HT2B-mediated ICC proliferation requires phospholipase C and protein kinase C gamma (PKCγ).

Area of Science:

  • Gastroenterology
  • Cell Biology
  • Molecular Biology

Background:

  • The 5-hydroxytryptamine receptor 2B (5-HT2B) is a Gq/11 protein-coupled receptor involved in cell proliferation.
  • 5-HT2B receptors are present on interstitial cells of Cajal (ICC) in the gastrointestinal tract, regulating ICC proliferation.

Purpose of the Study:

  • To investigate the specific mitogenic signal transduction pathway activated by the 5-HT2B receptor in ICC.
  • To identify key molecular players in 5-HT2B receptor-mediated ICC proliferation.

Main Methods:

  • Primary mouse small intestine cell cultures were used.
  • Experiments involved receptor agonist stimulation and specific pathway inhibitors (e.g., U73122, Xestospongin C, Gö6976, Gö6983).
  • Single-cell PCR and studies using PKCgamma knockout mice were performed.

Main Results:

  • 5-HT2B receptor activation by BW723C86 stimulated ICC proliferation.
  • Inhibition of phospholipase C and inositol 1,4,5-trisphosphate receptors blocked proliferation.
  • PKC inhibitors blocked proliferation, with PKCgamma identified as crucial via studies in PKCgamma(-/-) mice.

Conclusions:

  • 5-HT2B receptor-mediated ICC proliferation is dependent on phospholipase C, intracellular calcium, and specifically protein kinase C gamma (PKCγ).
  • PKCγ plays a critical role in regulating ICC cellular proliferation in response to 5-HT2B receptor activation.

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