Metabolic Biology Graduate Program, University of California Berkeley, Berkeley, CA 94720, USA.
Department of Nutritional Sciences & Toxicology, University of California Berkeley, Berkeley, CA 94720, USA.
Int J Mol Sci. 2023 Aug 11;24(16):12665. doi: 10.3390/ijms241612665.
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 (PIP) to phosphatidylinositol 3,4,5-triphosphate (PIP), 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 gene.
PIK3R1（也称为 p85α）是磷酸肌醇 3-激酶（PI3Ks）的调节亚基。PI3K 是一个由调节亚基和催化亚基组成的异源二聚体，将磷脂酰肌醇磷酸化为参与调节代谢稳态的二级信号分子。PI3K 将磷脂酰肌醇 4,5-二磷酸（PIP）转化为磷脂酰肌醇 3,4,5-三磷酸（PIP），将蛋白激酶 AKT 募集到细胞膜的内叶以被激活并参与各种代谢功能。PIK3R1 稳定并抑制 p110 催化活性，并作为衔接蛋白与胰岛素受体底物（IRS）蛋白和生长因子受体相互作用。因此，PIK3R1 的突变或 PIK3R1 的表达改变可能调节 PI3K 的活性，并导致显著的代谢后果。有趣的是，最近的研究还发现了 PIK3R1 的 PI3K 非依赖性功能。总的来说，在本文中，我们将提供对 PIK3R1 代谢功能的最新综述，包括使用动物模型研究 PIK3R1 在各种代谢组织中的作用、调节 PIK3R1 活性的机制以及人类基因突变的研究。
