The regulatory subunits of PI3K,p85α and p85β,differentially affect BRD7-mediated regulation of insulin signaling

• 作者: Junsik M.Lee Renyan Liu Sang Won Park
• 来源期刊: 分子细胞生物学报（英文版）
• 年，卷（期）: 2021,（12）
• 所属期刊栏目: Articles
• 页码范围: 889-901
• 页数: 13页
• 语种: 英文
• DOI: 10.1093/jmcb/mjab073

摘要

Bromodomain-containing protein 7 (BRD7) has been shown to interact with the regulatory subunit of phosphatidylinositol 3-kinase(PI3K),p85,in the insulin signaling pathway.Here,we show that upregulation of hepatic BRD7 improves glucose homeostasis even in the absence of either p85 isoform,p85α or p85β.However,BRD7 leads to differential activation of downstream effector proteins in the insulin signaling pathway depending on which isoform of p85 is present.In the presence of only p85α,BRD7 over-expression increases phosphorylation of insulin receptor (IR) upon insulin stimulation,without increasing the recruitment of p85 to IR substrate.Overexpression of BRD7 also increases activation of Akt in response to insulin,but does not affect basal phosphor-ylation levels of Akt.Meanwhile,the phosphorylation of glycogen synthase kinase 3β (GSK3β) is increased by overexpression of BRD7.On the other hand,in the presence of only p85β,BRD7 overexpression does not affect phosphorylation levels of IR,and Akt phosphorylation is not affected by insulin stimulation following BRD7 upregulation.However,BRD7 overexpression leads to in-creased basal phosphorylation levels of Akt and GSK3β.These data demonstrate that BRD7's action on glucose homeostasis does not require the presence of both p85 isoforms,and p85α and p85β have unique roles in insulin signaling in the liver.