Rajala Ammaji, Wang Yuhong, Abcouwer Steven F, Gardner Thomas W, Rajala Raju V S
Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
Oncotarget. 2017 Dec 17;9(2):1505-1523. doi: 10.18632/oncotarget.23351. eCollection 2018 Jan 5.
Protein phosphatases are a group of universal enzymes that are responsible for the dephosphorylation of various proteins and enzymes in cells. Cellular signal transduction events are largely governed by the phosphorylation of key proteins. The length of cellular response depends on the activation of protein phosphatase that dephosphorylates the phosphate groups to halt a biological response, and fine-tune the defined cellular outcome. Dysregulation of these phosphatase(s) results in various disease phenotypes. The retina is a post-mitotic tissue, and oncogenic tyrosine and serine/ threonine kinase activities are important for retinal neuron survival. Aberrant activation of protein phosphatase(s) may have a negative effect on retinal neurons. In the current study, we characterized tumor suppressor protein phosphatase 2 (PP2A), a major serine/ threonine kinase with a broad substrate specificity. Our data suggest that PP2A is developmentally regulated in the retina, localized predominantly in the inner retina, and expressed in photoreceptor inner segments. Our findings indicate that PKCα and mTOR may serve as PP2A substrates. We found that light regulates PP2A activity. Our studies also suggest that rhodopsin regulates PP2A and its substrate(s) dephosphorylation. PP2A substrate phosphorylation is increased in mice lacking the A-subunit of PP2A. However, there is no accompanying effect on retina structure and function. Together, our findings suggest that controlling the activity of PP2A in the retina may be neuroprotective.
蛋白磷酸酶是一类普遍存在的酶，负责细胞内各种蛋白质和酶的去磷酸化。细胞信号转导事件在很大程度上受关键蛋白质磷酸化的调控。细胞反应的持续时间取决于蛋白磷酸酶的激活，该酶使磷酸基团去磷酸化以终止生物反应，并微调特定的细胞结果。这些磷酸酶的失调会导致各种疾病表型。视网膜是一种有丝分裂后组织，致癌性酪氨酸和丝氨酸/苏氨酸激酶活性对视网膜神经元的存活很重要。蛋白磷酸酶的异常激活可能对视网膜神经元产生负面影响。在本研究中，我们对肿瘤抑制蛋白磷酸酶2（PP2A）进行了表征，它是一种具有广泛底物特异性的主要丝氨酸/苏氨酸激酶。我们的数据表明，PP2A在视网膜中受到发育调控，主要定位于视网膜内层，并在光感受器内节中表达。我们的研究结果表明，PKCα和mTOR可能是PP2A的底物。我们发现光可调节PP2A的活性。我们的研究还表明，视紫红质可调节PP2A及其底物的去磷酸化。在缺乏PP2A A亚基的小鼠中，PP2A底物的磷酸化增加。然而，对视网膜结构和功能没有伴随影响。总之，我们的研究结果表明，控制视网膜中PP2A的活性可能具有神经保护作用。
