β-Arrestins在胰岛素／胰岛素样生长因子-1信号转导中的作用  

Role of β-arrestins in regulating insulin and insulin-like growth factor 1 signal transduction

作　　者：冯晓桃[1] 刘毅[1] 王文健[1] 

机构地区：[1]复旦大学华山医院中西医结合研究所,上海200040

出　　处：《国际内分泌代谢杂志》2010年第2期106-109,共4页International Journal of Endocrinology and Metabolism

摘　　要：β—Arrestins是G蛋白耦联受体信号转导通路的负调节因子，越来越多的证据表明，β-arrestins也能作用于细胞内的多种信号分子，调节胰岛素／胰岛素样生长因子一1（IGF一1）信号转导通路。在胰岛素的刺激下，β—arrestin2能够募集蛋白激酶B（Akt）和酪氨酸激酶Src到胰岛素受体，从而调节胰岛素介导的糖代谢效应；而β-arrestin1则与胰岛素受体底物一1（IRS一1）竞争性结合泛素连接酶Mdm2，从而减少IRS一1的泛素化和降解，促进磷脂酰肌醇3激酶（P13K）通路的信号转导。在IGF一1介导的信号转导通路中，β—arrestin1结合并介导了IGF一1受体（IGF一1R）的内吞，促进胞外信号调节激酶活化，正性调节丝裂原活化蛋白激酶通路。此外，t3-arrestin1与IGF一1R相耦联后，能越过信号分子IRS一1而激活P13K，进而活化Akt，表现出对P13K途径的正性调控作用。β-Arrestins are well-known negative regulators of G-protein-coupled receptor signaling, but accumulating evidence shows that β-arrestins also function as scaffold proteins that interact with several cytoplasmic proteins and modulate insulin/insulin-like growth factor 1 （ IGF-1 ） signal cascades. Upon stimulation by insulin, β3-arrestin 2 scaffolds protein kinase B （Akt） and Src to insulin receptor, thus regulating the glucose metabolic actions of insulin ;while β-arrestin 1 and insulin receptor substrate-I （IRS-1） competitively bind to Mdm2, an E3 ubiquitinhgase, thus inhibiting insulin-induced ubiquitination and degradation of IRS-1, which promotes phosphatidylinositol-3 kinase（PI3K） pathway by insulin. In IGF-1 signaling pathway, β-arrestin 1 targets IGF-1 receptor for endocytosis,then activates extracellular signal-regulated kinases,thus positively mediating mitogen-activated protein kinase pathway. Moreover, β-arrestin 1 scaffolds and recruits IGF-1 receptor to PI3 K in an IGF-l-dependent manner, thus mediates activation of PI3 K and Akt, showing positive effect on PI3K signaling.

关 键 词：Β-ARRESTIN 胰岛素 胰岛素样生长因子-1 信号转导 胰岛素抵抗 

分 类 号：R587.1[医药卫生—内分泌]