Abstract

Proline-rich Akt substrate of 40 kD (PRAS40) is not only the substrate of protein kinase B (PKB/Akt), but also the binding protein of 14-3-3 protein. PRAS40 is expressed in a variety of tissues in vivo and has multiple phosphorylation sites, which its activity is closely related to phosphorylation. Studies have shown that PRAS40 is involved in regulating cell growth, cell apoptosis, oxidative stress, autophagy and angiogenesis, as well as various of signalling pathways such as mammalian target of mammalian target rapamycin (mTOR), protein kinase B (PKB/Akt), nuclear factor kappa-B(NF-κB), proto-oncogene serine/threonine-protein kinase PIM-1(PIM1) and pyruvate kinase M2 (PKM2). The interactive roles between PRAS40 and these signal proteins were analysed by bioinformatics in this paper. Moreover, it is of great necessity for analyse the important roles of PRAS40 in some human diseases including cardiovascular disease, ischaemia-reperfusion injury, neurodegenerative disease, cancer, diabetes and other metabolic diseases. Finally, the effects of miRNA on the regulation of PRAS40 function and the occurrence and development of PRAS40-related diseases are also discussed. Overall, PRAS40 is expected to be a drug target and provide a new treatment strategy for human diseases.

摘要

40 kD的富含脯氨酸Akt底物（PRAS40）不仅是蛋白激酶B（PKB/Akt）的底物，也是14-3-3蛋白的结合蛋白。PRAS40在体内多种组织中表达并且具有多个磷酸化位点，其活性与磷酸化密切相关。研究表明，PRAS40参与调节细胞生长、细胞凋亡、氧化应激、自噬和血管生成，以及哺乳动物靶标雷帕霉素（mTOR）、蛋白激酶B（PKB/Akt）、核因子 kappa-B（NF-κB）、原癌基因丝氨酸/苏氨酸蛋白激酶 PIM-1（PIM1）和丙酮酸激酶 M2（PKM2）。本文通过生物信息学分析了PRAS40与这些信号蛋白之间的相互作用。此外，分析PRAS40在心血管疾病、缺血再灌注损伤、神经退行性疾病、癌症、糖尿病等代谢性疾病等人类疾病中的重要作用也很有必要。最后，还讨论了miRNA对PRAS40功能调控的影响以及PRAS40相关疾病的发生发展。总体而言，PRAS40有望成为药物靶点，为人类疾病提供新的治疗策略。