Dahal Arya, Hinton Shantá D
Department of Biology, Integrated Science Center, College of William and Mary, 540 Landrum Drive, Williamsburg, VA 23185, U.S.A.
Biochem Soc Trans. 2017 Apr 15;45(2):381-387. doi: 10.1042/BST20160273.
Mitogen-activated protein kinases (MAPKs) are essential players in important neuronal signaling pathways including neuronal development, plasticity, survival, learning, and memory. The inactivation of MAPKs is tightly controlled by MAPK phosphatases (MKPs), which also are important regulators of these neuronal processes. Considering that MAPKs and MKPs are major players in neuronal signaling, it follows that their misregulation is pivotal in neurodegenerative diseases such as Alzheimer's, Huntington's, Parkinson's, and amyotrophic lateral sclerosis. In contrast, the actions of their noncatalytic homologs, or pseudoenzymes, have received minimal attention as important regulators in neuronal signaling pathways and relevant diseases. There is compelling evidence, however, that pseudophosphatases, such as STYX (phospho-serine-threonine/tyrosine-binding protein) and MAPK-STYX (MK-STYX), are integral signaling molecules in regulating pathways involved in neuronal developmental processes such as neurite outgrowth. Here, we discuss how the dynamics of MK-STYX in the stress response pathway imply that this unique member of the MKP subfamily has the potential to have a major role in neuronal signaling. We further compare the actions of STYX in preventing neurite-like outgrowths and MK-STYX in inducing neurite outgrowths. The roles of these pseudophosphatases in neurite outgrowth highlight their emergence as important candidates to investigate in neurodegenerative disorders and diseases.
丝裂原活化蛋白激酶（MAPKs）是重要神经元信号通路中的关键参与者，这些信号通路包括神经元发育、可塑性、存活、学习和记忆。MAPKs的失活受到MAPK磷酸酶（MKPs）的严格控制，MKPs也是这些神经元过程的重要调节因子。鉴于MAPKs和MKPs是神经元信号传导的主要参与者，因此它们的失调在诸如阿尔茨海默病、亨廷顿病、帕金森病和肌萎缩侧索硬化等神经退行性疾病中起着关键作用。相比之下，它们的非催化同源物或假酶在神经元信号通路和相关疾病中作为重要调节因子的作用却很少受到关注。然而，有确凿的证据表明，假磷酸酶，如STYX（磷酸丝氨酸-苏氨酸/酪氨酸结合蛋白）和MAPK-STYX（MK-STYX），是调节神经元发育过程（如神经突生长）相关信号通路中不可或缺的信号分子。在这里，我们讨论了应激反应途径中MK-STYX的动态变化如何表明MKP亚家族的这一独特成员在神经元信号传导中可能发挥重要作用。我们进一步比较了STYX在阻止神经突样生长方面的作用和MK-STYX在诱导神经突生长方面的作用。这些假磷酸酶在神经突生长中的作用突出了它们作为神经退行性疾病和病症研究重要候选物的地位。
