Erythropoietin activates Phosphoinositide-3-kinase (PI3K)
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PI3K can bind the activated EPO receptor (EPOR) by three different mechanisms: direct binding to phospho-Y479 of the EPOR, indirect binding via phosphorylated IRS2 bound to the EPOR, and indirect binding via phosphorylated GAB1 bound to the EPOR (Bouscary et al. 2003, Schmidt et al. 2004, reviewed in Kuhrt and Wojchowski 2015). PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate to yield phosphatidylinositol 3,4,5-trisphosphate which recruits AKT1 to the membrane.
PI3K(磷脂酰肌醇3激酶)可通过三种不同的机制与激活的促红细胞生成素受体(EPOR)结合:直接与EPOR上的磷酸化Y479位点结合、通过与EPOR结合的磷酸化IRS2(胰岛素受体底物2)间接结合,以及通过与EPOR结合的磷酸化GAB1(生长因子结合蛋白1)间接结合(Bouscary等,2003年,Schmidt等,2004年,详见Kuhrt和Wojchowski,2015年综述)。PI3K将磷脂酰肌醇4,5-二磷酸磷酸化为磷脂酰肌醇3,4,5-三磷酸,从而募集AKT1(丝氨酸/苏氨酸激酶)至细胞膜。
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