Identification and localization of a skeletal muscle secrotonin 5-HT2A receptor coupled to the Jak/STAT pathway
Identification and localization of a skeletal muscle secrotonin 5-HT2A receptor coupled to the Jak/STAT pathway
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DOI：
10.1074/jbc.272.23.14825
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发表时间：
1997-06-06
影响因子：
4.8
通讯作者：
Girard, J
中科院分区：
文献类型：
--
作者：
GuilletDeniau, I;Burnol, AF;Girard, J
神经递质5-羟色胺通过与多种受体亚型结合介导多种外周和中枢生理效应（威尔金森，L. O.，和Dourish，C. T.（1991）血清素受体亚型：基础和临床方面（Peroutka，S. J.，艾德编）第15卷，第150页。147-210，Wiley-Liss，纽约）。其中，已知血清素5-HT 2A受体激活磷脂酶C-P第二信使途径（Peroutka，S. J.（1995）Trends Neurosci. 18，68-69）。我们在大鼠骨骼肌成肌细胞中鉴定并定位了一种功能性5-羟色胺5-HT 2A受体。该受体在质膜上、成肌细胞中和收缩肌管中的T-小管水平上检测到。5-羟色胺与其受体的结合增加了与肌源性分化有关的基因的表达。出乎意料的是，5-HT 2A 1受体能够激活另一种信号传导途径;它响应于5-羟色胺而触发Jak 2激酶的快速和短暂的酪氨酸磷酸化。Jak 2自身磷酸化之后是STAT 3（信号转导子和转录激活子）的酪氨酸磷酸化及其易位到细胞核中。我们还发现5-HT 2A受体和STAT 3与Jak 2共沉淀，表明它们是物理相关的。我们的结论是，5-羟色胺5-HT 2A受体在骨骼肌成肌细胞中鉴定能够激活细胞因子使用的细胞内磷酸化途径。T-小管中5-羟色胺受体的存在表明5-羟色胺在兴奋-收缩偶联中的作用和（或）在骨骼肌纤维修复中的作用。
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-P 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.