CAJ | 학술논문

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-1(IGF-1)信号转导通路.在胰岛素的刺激下,β-arrestin 2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-arrestin 1则与胰岛素受体底物-1(IRS-1)竞争性结合泛素连接酶Mdm2,从而减少IRS-1的泛素化和降解,促进磷脂酰肌醇3激酶(PI3K)通路的信号转导.在IGF-1介导的信号转导通路中,β-arrestin 1结合并介导了IGF-1受体(IGF-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,β-arrestin 1与IGF-1R相耦联后,能越过信号分子IRS-1而激活PI3K,进而活化Akt,表现出对P13K途径的正性调控作用.
β-Arrestins시G단백우련수체신호전도통로적부조절인자,월래월다적증거표명,β-arrestins야능작용우세포내적다충신호분자,조절이도소/이도소양생장인자-1(IGF-1)신호전도통로.재이도소적자격하,β-arrestin 2능구모집단백격매B(Akt)화락안산격매Src도이도소수체,종이조절이도소개도적당대사효응;이β-arrestin 1칙여이도소수체저물-1(IRS-1)경쟁성결합범소련접매Mdm2,종이감소IRS-1적범소화화강해,촉진린지선기순3격매(PI3K)통로적신호전도.재IGF-1개도적신호전도통로중,β-arrestin 1결합병개도료IGF-1수체(IGF-1R)적내탄,촉진포외신호조절격매활화,정성조절사렬원활화단백격매통로.차외,β-arrestin 1여IGF-1R상우련후,능월과신호분자IRS-1이격활PI3K,진이활화Akt,표현출대P13K도경적정성조공작용.
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 stimu-lation by insulin, β-arrestin 2 scaffolds protein kinase B (Akt) and Src to insulin receptor, thus regulating the glucose metabolic actions of insulin;while 13-arrestin 1 and insulin receptor substrate-1 (IRS-1) competitively bind to Mdm2, an E3 ubiquitinligase, 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-ar-restin 1 targets IGF-1 receptor for endocytosis,then activates extracellular signal-regulated kinases,thus posi-tively mediating mitogen-activated protein kinase pathway.Moreover, β-arrestin 1 scaffolds and recruits IGF-1 receptor to PI3 K in an IGF-1-dependent manner, thus mediates activation of PI3K and Akt, showing positive effect on PBK signaling.