| First Author | Launay JM | Year | 1996 |
| Journal | J Biol Chem | Volume | 271 |
| Issue | 6 | Pages | 3141-7 |
| PubMed ID | 8621713 | Mgi Jnum | J:39559 |
| Mgi Id | MGI:86840 | Doi | 10.1074/jbc.271.6.3141 |
| Citation | Launay JM, et al. (1996) Ras involvement in signal transduction by the serotonin 5-HT2B receptor. J Biol Chem 271(6):3141-7 |
| abstractText | The family of serotonin 5-HT2 receptors stimulates the phospholipase C second messenger pathway via the alpha 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, Galphaq, -beta, or -gamma2 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. |
