Protein Phosphatases and Proinflammatory Cytokines

描述（由申请人提供）：蛋白磷酸酶4（PP 4）是一种蛋白质 磷酸酶2A（PP 2A）相关的丝氨酸/苏氨酸磷酸酶。PP 2A参与 调节多种细胞过程，如细胞信号传导、细胞周期 调节，凋亡和肿瘤发生;然而，对肿瘤的发生知之甚少。 PP 4的功能。PP 2A的许多上述功能是基于 使用冈田酸的研究，冈田酸是一种以前认为是 PP 2A特异性，但现在已知在相似浓度下抑制PP 4。 因此，分配给PP 2A的先前识别的功能中的一些可以在PP 2A中被执行。 这就是PP 4的功能。 PP 4结合并激活Rel/NF-κ B蛋白。Rel/NF-κ B蛋白是关键的 参与过多细胞反应的分子，如基因 调节，凋亡，细胞周期，细胞增殖，肿瘤发生， 炎症和细胞粘附/迁移。我们最近的研究结果也表明 PP 4激活cJun N-末端激酶（JNK）。JNK亚组属于 丝裂原活化蛋白激酶（MAPK）超家族。JNK激酶级联是 参与细胞凋亡、分化、细胞增殖、肿瘤发生， 各种应激反应，如炎症反应和心脏 缺血/再灌注了解PP 4的功能和调节， 以及PP 4激活NF-κ B/JNK的潜在机制将导致 更好地理解NF-κ B、JNK和PP 4信号通路。具体 目的是：（1）研究PP 4的调控和功能，（2） 确定PP 4在NF-κ B活化中的作用，以及（3）确定PP 4在NF-κ B活化中的作用。 PP 4在JNK激活中的作用，本研究所获得的信息应能提供 更好地设计炎症治疗药物的重要信息 疾病、癌症和心脏病。

DESCRIPTION (provided by applicant): Protein phosphatase 4 (PP4) is a protein phosphatase 2A (PP2A)-related serine/threonine phosphatase. PP2A is involved in regulating diverse cellular processes such as cell signaling, cell cycle regulation, apoptosis, and tumorigenesis; however, little is known about the functions of PP4. Many of the above functions identified for PP2A were based on the studies using okadaic acid, an inhibitor previously thought to be PP2A-specific, but now known to inhibit PP4 at similar concentrations. Therefore, some of the previously identified functions assigned to PP2A may in fact be the functions for PP4. PP4 binds to and activates Rel/NF-KB proteins. Rel/NF-KB proteins are pivotal molecules that are involved in a plethora of cellular responses such as gene regulation, apoptosis, cell cycle, cell proliferation, oncogenesis, inflammation, and cell adhesion/migration. Our recent results also indicate that PP4 activates cJun N-terminal kinase (JNK). JNK subgroup belongs to the mitogen-activated protein kinase (MAPK) superfamily. JNK kinase cascade is involved in apoptosis, differentiation, cell proliferation, oncogenesis, and various stress responses such as inflammatory responses and heart ischemia/reperfusion. Understanding the functions and regulation of PP4, as well as the underlying mechanisms of NF-KB/JNK activation by PP4 will lead to a better understanding of the NF-KB, JNK and PP4 signaling pathways. The specific aims are the following: (1) to study the regulation andfunction of PP4, (2) to determine the role of PP4 in NF-KB activation, and (3) to determine the role of PP4 in JNK activation, The information derived from this study should provide important information for a better design of therapeutic drugs for inflammatory diseases, cancers, and cardiac diseases.