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PAQR3 Modulates Insulin Signaling by Shunting Phosphoinositide 3-Kinase p110 alpha to the Golgi Apparatus

文献类型:期刊论文

作者Wang, Xiao; Wang, Lingdi; Zhu, Lu; Pan, Yi(潘怡); Xiao, Fei; Liu, Weizhong; Wang, ZhenZhen(王甄真); Guo, Feifan(郭非凡); Liu, Yong(刘勇); Thomas, Walter G.
刊名DIABETES
出版日期2013
卷号62期号:2页码:444-456
英文摘要Phosphoinositide 3-kinase (PI3K) mediates insulin actions by relaying signals from insulin receptors (IRs) to downstream targets. The p110 alpha catalytic subunit of class IA PI3K is the primary insulin-responsive PI3K implicated in insulin signaling. We demonstrate here a new mode of spatial regulation for the p110 alpha subunit of PI3K by PAQR3 that is exclusively localized in the Golgi apparatus. PAQR3 interacts with p110 alpha, and the intracellular targeting of p110 alpha to the Golgi apparatus is reduced by PAQR3 downregulation and increased by PAQR3 overexpression. Insulin-stimulated PI3K activity and phosphoinositide (3,4,5)-triphosphate production are enhanced by Paqr3 deletion and reduced by PAQR3 overexpression in hepatocytes. Deletion of Paqr3 enhances insulin-stimulated phosphorylation of AKT and glycogen synthase kinase 3 beta, but not phosphorylation of IR and IR substrate-1 (IRS-1), in hepatocytes, mouse liver, and skeletal muscle. Insulin-stimulated GLUT4 translocation to the plasma membrane and glucose uptake are enhanced by Paqr3 ablation. Furthermore, PAQR3 interacts with the domain of p110 alpha involved in its binding with p85, the regulatory subunit of PI3K. Overexpression of PAQR3 dose-dependently reduces the interaction of p85 alpha with p110 alpha. Thus, PAQR3 negatively regulates insulin signaling by shunting cytosolic p110 alpha to the Golgi apparatus while competing with p85 subunit in forming a PI3K complex with p110 alpha. Diabetes 62:444-456, 2013
类目[WOS]Endocrinology & Metabolism
关键词[WOS]PHOSPHATIDYLINOSITOL 3-KINASE ; METABOLIC-REGULATION ; EMBRYONIC LETHALITY ; PI 3-KINASE ; B-CELL ; RKTG ; SUBUNIT ; DOMAINS ; KINASE ; GROWTH
收录类别SCI
语种英语
WOS记录号WOS:000314263600020
版本出版稿
源URL[http://202.127.25.144/handle/331004/62]  
专题中国科学院上海生命科学研究院营养科学研究所_信号转导与营养相关疾病研究组
中国科学院上海生命科学研究院营养科学研究所_代谢的遗传与营养调控研究组
中国科学院上海生命科学研究院营养科学研究所_糖脂代谢与调控研究组
推荐引用方式
GB/T 7714
Wang, Xiao,Wang, Lingdi,Zhu, Lu,et al. PAQR3 Modulates Insulin Signaling by Shunting Phosphoinositide 3-Kinase p110 alpha to the Golgi Apparatus[J]. DIABETES,2013,62(2):444-456.
APA Wang, Xiao.,Wang, Lingdi.,Zhu, Lu.,Pan, Yi.,Xiao, Fei.,...&Chen, Yan.(2013).PAQR3 Modulates Insulin Signaling by Shunting Phosphoinositide 3-Kinase p110 alpha to the Golgi Apparatus.DIABETES,62(2),444-456.
MLA Wang, Xiao,et al."PAQR3 Modulates Insulin Signaling by Shunting Phosphoinositide 3-Kinase p110 alpha to the Golgi Apparatus".DIABETES 62.2(2013):444-456.

入库方式: OAI收割

来源:上海营养与健康研究所

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