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 

机构地区：[1]Division of Endocrinology,Boston Children’s Hospital,Harvard Medical School,Boston,MA 02115,USA

出　　处：《Journal of Molecular Cell Biology》2021年第12期889-901,共13页分子细胞生物学报（英文版）

基　　金：This work was supported by the National Institutes of Health(R01DK118244);the American Heart Association(18IPA34140057);the American Diabetes Association(1-17-IBS-104);the faculty start up fund provided to S.W.P.from Boston Children’s Hospital.

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 homeostasiseven in the absence of either p85 isoform, p85a or p85b. However, BRD7 leads to differential activation of downstream effectorproteins in the insulin signaling pathway depending on which isoform of p85 is present. In the presence of only p85a, BRD7 overexpression increases phosphorylation of insulin receptor (IR) upon insulin stimulation, without increasing the recruitment of p85to IR substrate. Overexpression of BRD7 also increases activation of Akt in response to insulin, but does not affect basal phosphorylation levels of Akt. Meanwhile, the phosphorylation of glycogen synthase kinase 3b (GSK3b) is increased by overexpression ofBRD7. On the other hand, in the presence of only p85b, BRD7 overexpression does not affect phosphorylation levels of IR, and Aktphosphorylation is not affected by insulin stimulation following BRD7 upregulation. However, BRD7 overexpression leads to increased basal phosphorylation levels of Akt and GSK3b. These data demonstrate that BRD7’s action on glucose homeostasis doesnot require the presence of both p85 isoforms, and p85a and p85b have unique roles in insulin signaling in the liver.

关 键 词：PI3K BRD7 AKT insulin signaling 

分 类 号：R58[医药卫生—内分泌]