Identification and localization of a skeletal muscle secrotonin 5-HT2A receptor coupled to the Jak/STAT pathway.
The neurotransmitter serotonin mediates a wide variety of peripheral and central physiological effects through the binding to multiple receptor subtypes (Wilkinson, L. O., and Dourish, C. T. (1991) in Serotonin Receptor Subtypes: Basic and Clinical Aspects (Peroutka, S. J., ed) Vol. 15, pp.147-210, Wiley-Liss, New York). Among them, serotonin 5-HT2A ... receptors are known to activate the phospholipase C-beta second messenger pathway (Peroutka, S. J. (1995) Trends Neurosci. 18, 68-69). We identified and localized in rat skeletal muscle myoblasts a functional serotonin 5-HT2A receptor. This receptor was detected on the plasma membrane, in myoblasts, and at the level of T-tubules in contracting myotubes. Binding of serotonin to its receptor increases the expression of genes involved in myogenic differentiation. Unexpectedly, the 5-HT2A receptor is able to activate another signaling pathway; it triggers a rapid and transient tyrosine phosphorylation of Jak2 kinase in response to serotonin. Jak2 auto-phosphorylation is followed by the tyrosine phosphorylation of STAT3 (signal transducers and activators of transcription) and its translocation into the nucleus. We also find that the 5-HT2A receptor and STAT3 co-precipitate with Jak2, indicating that they are physically associated. We conclude that the serotonin 5-HT2A receptor identified in skeletal muscle myoblasts is able to activate the intracellular phosphorylation pathway used by cytokines. The presence of serotonin receptors in T-tubules suggests a role for serotonin in excitation-contraction coupling and (or) an effect in skeletal muscle fiber repairing.
Mesh Terms:
Animals, Base Sequence, Cell Membrane, Cells, Cultured, DNA-Binding Proteins, Fetus, Glucose Transporter Type 1, Glucose Transporter Type 2, Janus Kinase 2, Molecular Sequence Data, Monosaccharide Transport Proteins, Muscle, Skeletal, Myogenin, Phosphorylation, Polymerase Chain Reaction, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Rats, Receptor, Serotonin, 5-HT2A, Receptors, Serotonin, STAT3 Transcription Factor, Serotonin, Signal Transduction, Trans-Activators, Transcription, Genetic
Animals, Base Sequence, Cell Membrane, Cells, Cultured, DNA-Binding Proteins, Fetus, Glucose Transporter Type 1, Glucose Transporter Type 2, Janus Kinase 2, Molecular Sequence Data, Monosaccharide Transport Proteins, Muscle, Skeletal, Myogenin, Phosphorylation, Polymerase Chain Reaction, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Rats, Receptor, Serotonin, 5-HT2A, Receptors, Serotonin, STAT3 Transcription Factor, Serotonin, Signal Transduction, Trans-Activators, Transcription, Genetic
J. Biol. Chem.
Date: Jun. 06, 1997
PubMed ID: 9169451
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