Phosphoinositide 3-kinase: friend and foe in cardiovascular disease.
Phosphoinositide 3-kinase: friend and foe in cardiovascular disease.
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DOI：
10.3389/fphar.2015.00169
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发表时间：
2015
影响因子：
5.6
通讯作者：
Li M
中科院分区：
文献类型：
--
作者：
Ghigo A;Li M
I类磷酸肌醇3-激酶（PI 3 Ks）是由细胞膜受体（受体酪氨酸激酶（RTK）或G蛋白偶联受体（GPCR））激活的脂质激酶家族，以催化脂质第二信使磷脂酰肌醇（3，4，5）-三磷酸（PIP 3）的产生。这些酶参与控制细胞增殖、存活和迁移的多个下游细胞内信号传导途径。在心血管系统中，四种I类PI 3 K亚型PI 3 K α、PI 3 K β、PI 3 K δ和PI 3 K γ在不同的细胞亚群中差异表达，所述细胞亚群包括心肌细胞、成纤维细胞、内皮细胞和血管平滑肌细胞以及白细胞，这表明不同的PI 3 K同工酶具有特异性功能。在过去的几十年中，针对不同PI 3 K基因的遗传破坏研究已经阐明了特定同工酶对心脏和血管功能调节的贡献，突出了有益和适应不良的作用。最近出现了PI 3 K功能的新的复杂层，表明不同的PI 3 K亚型通过各种串扰事件相互连接，并且不仅可以作为激酶发挥作用，还可以作为协调心血管健康和疾病中关键信号体的支架蛋白。在这篇综述中，我们将总结在理解有害和有益的行动PI 3 K信号在心血管稳态的重大突破，我们将讨论最近解开的串扰和支架机制，以及较少的特点II类和III类PI 3 K亚型的作用。
Class I phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases activated by cell membrane receptors, either receptor tyrosine kinases (RTKs) or G protein–coupled receptors (GPCRs), to catalyze the production of the lipid second messenger phosphatidylinositol (3,4,5)-trisphosphate (PIP3). These enzymes engage multiple downstream intracellular signaling pathways controlling cell proliferation, survival and migration. In the cardiovascular system, the four class I PI3K isoforms, PI3Kα, PI3Kβ, PI3Kδ, and PI3Kγ are differentially expressed in distinct cell subsets which include cardiomyocytes, fibroblasts, endothelial, and vascular smooth muscle cells as well as leukocytes, suggesting specific functions for distinct PI3K isoenzymes. During the last decades, genetic disruption studies targeting different PI3K genes have elucidated the contribution of specific isoenzymes to cardiac and vascular function regulation, highlighting both beneficial and maladaptive roles. New layers of complexity in the function of PI3Ks have recently emerged, indicating that distinct PI3K isoforms are interconnected by various crosstalk events and can function not only as kinases, but also as scaffold proteins coordinating key signalosomes in cardiovascular health and disease. In this review, we will summarize major breakthroughs in the comprehension of detrimental and beneficial actions of PI3K signaling in cardiovascular homeostasis, and we will discuss recently unraveled cross-talk and scaffold mechanisms as well as the role of the less characterized class II and III PI3K isoforms.