Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
Mol Pain. 2013 Sep 8;9:46. doi: 10.1186/1744-8069-9-46.
Multiple protein kinases affect the responses of dorsal horn neurons through phosphorylation of synaptic receptors and proteins involved in intracellular signal transduction pathways, and the consequences of this modulation may be spinal central sensitization. In contrast, the phosphatases catalyze an opposing reaction of de-phosphorylation, which may also modulate the functions of crucial proteins in signaling nociception. This is an important mechanism in the regulation of intracellular signal transduction pathways in nociceptive neurons. Accumulated evidence has shown that phosphatase 2A (PP2A), a serine/threonine specific phosphatase, is implicated in synaptic plasticity of the central nervous system and central sensitization of nociception. Therefore, targeting protein phosphotase 2A may provide an effective and novel strategy for the treatment of clinical pain. This review will characterize the structure and functional regulation of neuronal PP2A and bring together recent advances on the modulation of PP2A in targeted downstream substrates and relevant multiple nociceptive signaling molecules.
多种蛋白激酶通过磷酸化突触受体和细胞内信号转导途径相关蛋白来影响背角神经元的反应，这种调节的后果可能是脊髓中枢敏化。相比之下，磷酸酶催化相反的去磷酸化反应，这也可能调节信号转导伤害感受中关键蛋白的功能。这是伤害感受神经元细胞内信号转导途径调节的重要机制。越来越多的证据表明，磷酸酶 2A（PP2A），一种丝氨酸/苏氨酸特异性磷酸酶，与中枢神经系统的突触可塑性和伤害感受的中枢敏化有关。因此，靶向蛋白磷酸酶 2A 可能为治疗临床疼痛提供一种有效和新颖的策略。本综述将描述神经元 PP2A 的结构和功能调节，并汇集 PP2A 在靶向下游底物和相关多种伤害感受信号分子中的调节的最新进展。
