Abstract：
c-Jun N-terminal kinases (JNKs) are stress-activated serine/threonine protein kinases belonging to the mitogen-activated protein kinase (MAPK) family. Among them, JNK3 is selectively expressed in the central nervous system, cardiac smooth muscle, and testis. In addition, it is the most responsive JNK isoform to stress stimuli in the brain, and it is involved in synaptic dysfunction, an essential step in neurodegenerative processes. JNK3 pathway is organized in a cascade of amplification in which signal transduction occurs by stepwise, highly controlled phosphorylation. Since different MAPKs share common upstream activators, pathway specificity is guaranteed by scaffold proteins such as JIP1 and β-arrestin2. To better elucidate the physiological mechanisms regulating JNK3 in neurons, and how these interactions may be involved in synaptic (dys)function, we used (i) super-resolution microscopy to demonstrate the colocalization among JNK3-PSD95-JIP1 and JNK3-PSD95-β-arrestin2 in cultured hippocampal neurons, and (ii) co-immunoprecipitation techniques to show that the two scaffold proteins and JNK3 can be found interacting together with PSD95. The protein-protein interactions that govern the formation of these two complexes, JNK3-PSD95-JIP1 and JNK3-PSD95-β-arrestin2, may be used as targets to interfere with their downstream synaptic events.
摘要：
c-JunN-末端激酶(JNKs)是应激活化的丝氨酸/苏氨酸蛋白激酶,属于丝裂原活化蛋白激酶(MAPK)家族。其中,JNK3在中枢神经系统中选择性表达，心脏平滑肌,和睾丸。此外,它是大脑中对压力刺激反应最敏感的JNK亚型，它与突触功能障碍有关，神经退行性过程中的重要步骤。JNK3通路以级联放大的方式组织，其中信号转导逐步发生，高度受控的磷酸化。由于不同的MAPK共享共同的上游激活器，JIP1和β-arrestin2等支架蛋白保证了通路的特异性。为了更好地阐明调节神经元JNK3的生理机制，以及这些相互作用如何参与突触（dys）功能，我们使用（i）超分辨率显微镜来证明JNK3-PSD95-JIP1和JNK3-PSD95-β-arrestin2在培养的海马神经元中的共定位，和（ii）共免疫沉淀技术，以显示两种支架蛋白和JNK3可以与PSD95相互作用。控制这两种复合物形成的蛋白质-蛋白质相互作用，JNK3-PSD95-JIP1和JNK3-PSD95-β-arrestin2可用作干扰其下游突触事件的靶标。
