Serotonin regulates 6-phosphofructo-1-kinase activity in a PLC-PKC-CaMK II- and Janus kinase-dependent signaling pathway
Serotonin regulates 6-phosphofructo-1-kinase activity in a PLC-PKC-CaMK II- and Janus kinase-dependent signaling pathway
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DOI：
10.1007/s11010-012-1462-0
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发表时间：
2013-01-01
影响因子：
4.3
通讯作者：
Sola-Penna, Mauro
中科院分区：
文献类型：
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作者：
Coelho, Wagner Santos;Sola-Penna, Mauro
5-羟色胺（5-HT）是一种参与调节许多生理和病理事件的激素。这种激素最有趣的特性之一是它能够上调有丝分裂。此外，5-HT刺激葡萄糖摄取并通过5-HT 2A受体上调PFK活性，导致PFK酪氨酸残基的磷酸化和PFK在骨骼肌内的细胞内再分布。本研究采用动力学评估、免疫沉淀和蛋白质印迹分析，研究了5-HT对骨骼肌6-磷酸果糖-1-激酶（PFK）调节作用中的一些信号中间体。我们的研究结果表明，5-HT通过磷脂酶C（PLC）刺激骨骼肌PFK。骨骼肌中PLC的激活导致蛋白激酶C（PKC）和钙调素的募集以及钙调素激酶II的刺激，钙调素激酶II在5-HT作用后与PFK相关。或者，当Janus激酶被抑制时，5-HT失去了上调PFK活性的能力，这表明5-HT能够通过募集不同的途径和控制PFK活性来控制小鼠骨骼肌中的糖酵解通量。
Serotonin (5-HT) is a hormone that has been implicated in the regulation of many physiological and pathological events. One of the most intriguing properties of this hormone is its ability to up-regulate mitosis. Moreover, 5-HT stimulates glucose uptake and up-regulates PFK activity through the 5-HT2A receptor, resulting in the phosphorylation of a tyrosine residue of PFK and the intracellular redistribution of PFK within skeletal muscle. The present study investigated some of the signaling intermediates involved in the effects of 5-HT on 6-phosphofructo-1-kinase (PFK) regulation from skeletal muscle using kinetic assessments, immunoprecipitation, and western blotting assays. Our results demonstrate that 5-HT stimulates PFK from skeletal muscle via phospholipase C (PLC). The activation of PLC in skeletal muscle leads to the recruitment of protein kinase C (PKC) and calmodulin and the stimulation of calmodulin kinase II, which associates with PFK upon 5-HT action. Alternatively, 5-HT loses its ability to up-regulate PFK activity when Janus kinase is inhibited, suggesting that 5-HT is able to control glycolytic flux in the skeletal muscle of mice by recruiting different pathways and controlling PFK activity.