The Role of PIK3R1 in Metabolic Function and Insulin Sensitivity.

The Role of PIK3R1 in Metabolic Function and Insulin Sensitivity.
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DOI:
10.3390/ijms241612665
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发表时间:
2023-08-11
影响因子:
5.6
通讯作者:
Wang, Jen-Chywan
Wang, Jen-Chywan
中科院分区:
生物学2区
文献类型:
--
作者:
Tsay, Ariel;Wang, Jen-Chywan

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PIK3R1(也称为 p85α)是磷酸肌醇 3-激酶 (PI3K) 的调节亚基。 PI3K 是调节亚基和催化亚基的异二聚体,可将磷脂酰肌醇磷酸化为参与调节代谢稳态的次级信号分子。 PI3K 将磷脂酰肌醇 4,5-二磷酸 (PIP2) 转化为磷脂酰肌醇 3,4,5-三磷酸 (PIP3),后者将蛋白激酶 AKT 招募到细胞膜内层被激活并参与各种代谢功能。 PIK3R1 稳定并抑制 p110 催化活性,并作为与胰岛素受体底物 (IRS) 蛋白和生长因子受体相互作用的接头。因此,PIK3R1 的突变或 PIK3R1 表达的改变可以调节 PI3K 的活性并导致显着的代谢结果。有趣的是,最近的研究还发现 PIK3R1 具有独立于 PI3K 的功能。总的来说,在本文中,我们将对 PIK3R1 的代谢功能进行最新的综述,包括使用动物模型对 PIK3R1 在各种代谢组织中的研究、调节 PIK3R1 活性的机制以及人类 PIK3R1 基因突变的研究。
PIK3R1 (also known as p85α) is a regulatory subunit of phosphoinositide 3-kinases (PI3Ks). PI3K, a heterodimer of a regulatory subunit and a catalytic subunit, phosphorylates phosphatidylinositol into secondary signaling molecules involved in regulating metabolic homeostasis. PI3K converts phosphatidylinositol 4,5-bisphosphate (PIP2) to phosphatidylinositol 3,4,5-triphosphate (PIP3), which recruits protein kinase AKT to the inner leaflet of the cell membrane to be activated and to participate in various metabolic functions. PIK3R1 stabilizes and inhibits p110 catalytic activity and serves as an adaptor to interact with insulin receptor substrate (IRS) proteins and growth factor receptors. Thus, mutations in PIK3R1 or altered expression of PIK3R1 could modulate the activity of PI3K and result in significant metabolic outcomes. Interestingly, recent studies also found PI3K-independent functions of PIK3R1. Overall, in this article, we will provide an updated review of the metabolic functions of PIK3R1 that includes studies of PIK3R1 in various metabolic tissues using animal models, the mechanisms modulating PIK3R1 activity, and studies on the mutations of human PIK3R1 gene.
通过p85α单体二聚体平衡对PI3K途径进行调节。
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