cAMP-dependent protein kinase regulates desensitization of the capsaicin receptor (VR1) by direct phosphorylation
cAMP-dependent protein kinase regulates desensitization of the capsaicin receptor (VR1) by direct phosphorylation
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DOI：
10.1016/s0896-6273(02)00802-4
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发表时间：
2002-08-15
期刊：
影响因子：
16.2
通讯作者：
Gereau, RW
中科院分区：
文献类型：
--
作者：
Bhave, G;Zhu, WG;Gereau, RW
辣椒素受体，VR1（也称为TRPV1），是一种表达在伤害性感觉神经元上的配体门控离子通道，对有害的热和化学刺激做出反应。感觉神经元中的辣椒素反应通过cAMP依赖性蛋白激酶（PKA）表现出强烈的增强作用。在这项研究中，我们证明，PKA减少VR1脱敏和直接磷酸化VR1。VR1胞质结构域的体外磷酸化、磷酸肽图谱和蛋白质测序描绘了几个候选PKA磷酸化位点。磷酸化位点突变体的电生理学分析清楚地指出Ser116作为负责VR1的PKA依赖性调节的残基。鉴于VR1和PKA在炎性疼痛超敏反应中的重要作用，VR1在Ser116处被PKA磷酸化可能代表了组织损伤后VR1功能调节的重要分子机制。
The capsaicin receptor, VR1 (also known as TRPV1), is a ligand-gated ion channel expressed on nociceptive sensory neurons that responds to noxious thermal and chemical stimuli. Capsaicin responses in sensory neurons exhibit robust potentiation by cAMP-dependent protein kinase (PKA). In this study, we demonstrate that PKA reduces VR1 desensitization and directly phosphorylates VR1. In vitro phosphorylation, phosphopeptide mapping, and protein sequencing of VR1 cytoplasmic domains delineate several candidate PKA phosphorylation sites. Electrophysiological analysis of phosphorylation site mutants clearly pinpoints Ser116 as the residue responsible for PKA-dependent modulation of VR1. Given the significant roles of VR1 and PKA in inflammatory pain hypersensitivity, VR1 phosphorylation at Ser116 by PKA may represent an important molecular mechanism involved in the regulation of VR1 function after tissue injury.