Ghigo Alessandra, Morello Fulvio, Perino Alessia, Hirsch Emilio
Molecular Biotechnology Center, Department of Genetics, Biology and Biochemistry, University of Torino, Torino, Italy.
Subcell Biochem. 2012;58:183-213. doi: 10.1007/978-94-007-3012-0_6.
In the last decade, the availability of genetically modified animals has revealed interesting roles for phosphoinositide 3-kinases (PI3Ks) as signaling platforms orchestrating multiple cellular responses, both in health and pathology. By acting downstream distinct receptor types, PI3Ks nucleate complex signaling assemblies controlling several biological process, ranging from cell proliferation and survival to immunity, cancer, metabolism and cardiovascular control. While the involvement of these kinases in modulating immune reactions and neoplastic transformation has long been accepted, recent progress from our group and others has highlighted new and unforeseen roles of PI3Ks in controlling cardiovascular function. Hence, the view is emerging that pharmacological targeting of distinct PI3K isoforms could be successful in treating disorders such as myocardial infarction and heart failure, besides inflammatory diseases and cancer. Currently, PI3Ks represent attractive drug targets for companies interested in the development of novel and safe treatments for such diseases. Numerous hit and lead compounds are now becoming available and, for some of them, clinical trials can be envisaged in the near future. In the following sections, we will outline the impact of specific PI3K isoforms in regulating different cellular contexts, including immunity, metabolism, cancer and cardiovascular system, both in physiological and disease conditions.
在过去十年中，转基因动物的出现揭示了磷脂酰肌醇3激酶（PI3Ks）作为协调多种细胞反应的信号平台在健康和病理过程中所起的有趣作用。通过作用于不同类型的受体下游，PI3Ks形成控制多种生物学过程的复杂信号组件，这些过程涵盖从细胞增殖、存活到免疫、癌症、代谢和心血管调节等各个方面。虽然这些激酶在调节免疫反应和肿瘤转化中的作用早已为人所知，但我们团队和其他团队最近的研究进展突出了PI3Ks在控制心血管功能方面新的、意想不到的作用。因此，一种新观点正在形成，即除了炎症性疾病和癌症外，针对不同PI3K亚型的药物靶向治疗可能成功用于治疗心肌梗死和心力衰竭等疾病。目前，对于有兴趣开发此类疾病新型安全治疗方法的公司而言，PI3Ks是有吸引力的药物靶点。现在有许多有潜力的化合物可供使用，其中一些有望在不久的将来开展临床试验。在接下来的章节中，我们将概述特定PI3K亚型在生理和疾病状态下调节不同细胞环境（包括免疫、代谢、癌症和心血管系统）中的作用。
