Ras Involvement in Signal Transduction by the Serotonin 5-HT2B Receptor (∗)

The family of serotonin 5-HT2 receptors stimulates the phospholipase C second messenger pathway via the α subunit of the Gq 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...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 1996-02, Vol.271 (6), p.3141-3147
Main Authors: Launay, Jean-Marie, Birraux, Guillaume, Bondoux, Dominique, Callebert, Jacques, Choi, Doo-Sup, Loric, Sylvain, Maroteaux, Luc
Format: Article
Language:English
Subjects:
Amphetamines - metabolism
Amphetamines - pharmacology
Animals
Carcinoid Tumor - metabolism
Carcinoid Tumor - pathology
Carcinoid Tumor - veterinary
Cell Line
Enzyme Activation
Gene Expression
GTP Phosphohydrolases - metabolism
GTP-Binding Proteins - metabolism
Humans
Immunohistochemistry
Kinetics
Mastomys natalensis
Mice
Muridae
ras Proteins
Receptor, Serotonin, 5-HT2B
Receptors, Serotonin - biosynthesis
Receptors, Serotonin - physiology
Recombinant Proteins - biosynthesis
Recombinant Proteins - metabolism
Ritanserin - pharmacology
Rodent Diseases
Second Messenger Systems
Serotonin - pharmacology
Serotonin Receptor Agonists - metabolism
Serotonin Receptor Agonists - pharmacology
Signal Transduction
Transfection
Type C Phospholipases - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The family of serotonin 5-HT2 receptors stimulates the phospholipase C second messenger pathway via the α subunit of the Gq 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 proto-oncogene product p21ras as measured by an increase in GTP-bound Ras in response to serotonin. Furthermore, 5-HT2B receptor stimulation activates p42mapk/p44mapk (ERK2/ERK1) mitogen-activated protein kinases as assayed by phosphorylation of myelin basic protein. Antibodies against p21ras, Gαq, -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 p21ras activation.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.271.6.3141