Ras involvement in signal transduction by the serotonin 5-HT2B receptor

Jean Marie Launay, Guillaume Birraux, Dominique Bondoux, Jacques Callebert, Doo Sup Choi, Sylvain Loric, Luc Maroteauxi

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111 Scopus citations

Abstract

The family of serotonin 5-HT2 receptors stimulates the phospholipase C second messenger pathway via the α subunit of the G(q) GTP-binding protein. Here, we show that agonist stimulation of the 5-HT2B receptor subtype stably expressed in the mouse fibroblast LMTK- cell line causes a rapid and transient activation of the protooncogene product p21(ras) as measured by an increase in GTP-bound Ras in response to serotonin. Furthermore, 5-HT2B receptor stimulation activates p42(mapk)/p44(mapk) (ERK2/ERK1) mitogen- activated protein kinases as assayed by phosphorylation of myelin basic protein. Antibodies against p21(ras), Gα(q), -β, or -γ2 subunits of the GTP-binding protein inhibit MAP kinase-dependent phosphorylation. The MAP kinase activation is correlated with a stimulation of cell division by serotonin. In addition to this mitogenic action, transforming activity of serotonin is mediated by the 5-HT2B receptor since its expression in LMTK- cells is absolutely required for foci formation and for these foci to form tumors in nude mice. Finally, we detected expression of the 5-HT2B receptor in spontaneous human and Mastomys natalensis carcinoid tumors and, similar to the 5-HT2B receptor transfected cells, the Mastomys tumor cells are also responsive to serotonin with similar coupling to p21(ras) activation.

Original languageEnglish (US)
Pages (from-to)3141-3147
Number of pages7
JournalJournal of Biological Chemistry
Volume271
Issue number6
DOIs
StatePublished - Feb 9 1996

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Launay, J. M., Birraux, G., Bondoux, D., Callebert, J., Choi, D. S., Loric, S., & Maroteauxi, L. (1996). Ras involvement in signal transduction by the serotonin 5-HT2B receptor. Journal of Biological Chemistry, 271(6), 3141-3147. https://doi.org/10.1074/jbc.271.6.3141