血清和糖皮质激素诱导的蛋白激酶在恶性肿瘤中的作用

Role of serum and glucocorticoid-induced protein kinases in malignant tumors

血清和糖皮质激素诱导的蛋白激酶(serum and glucocorticoid-induced protein kinase,SGK)是一种丝氨酸/苏氨酸双特异性蛋白激酶,由3种亚型(SGK1、SGK2及SGK3)组成,3个亚型具有高度同源性,但是功能各不相同。SGK的3种亚型与肿瘤生长、转移、自噬及上皮离子转运的调节有关。SGK与蛋白激酶B(PKB/AKT)有相似的结构、功能和底物特异性,与AKT一样,也是在磷脂酰肌醇3-激酶(PI3K)通路的下游被激活,该途径由3-磷酸肌醇依赖性蛋白激酶1(3-phosphate inositol dependent protein kinase 1,PDK1)和哺乳动物雷帕霉素靶蛋白复合体2(mammalian target of rapamycin complex 2,mTORC2)介导。PI3K可以通过依赖SGK,但不依赖蛋白激酶B(PKB/AKT)的机制在肿瘤的发生中起作用,在许多癌症中SGK表达水平显著增加已得到证实。因此,SGK可能是一个潜在的抗癌治疗靶点。

Serum and glucocorticoid-induced protein kinase(SGK)is a serine/threonine bispecific protein kinase,composed of 3 subtypes(SGK1,SGK2 and SGK3).The 3 subtypes are highly homologous,but have different functions.The 3 subtypes of SGK are related to the regulation of tumor growth,metastasis,autophagy,and epithelial ion transport.SGK is similar to protein kinase B(PKB/AKT)in structure,function and substrate specificity.Like AKT,it is also activated by the downstream of phosphatidylinositol 3-kinase(PI3K)pathway,which is mediated by 3-phosphate inositol dependent protein kinase 1(PDK1)and mammalian target of rapamycin complex 2(mTORC2).PI3K can play a role in tumorigenesis through a SGK-dependent but PKB/AKT-independent mechanism,and it has been confirmed that the expression of SGK is significantly increased in many cancers.Therefore,SGK may be a potential target for anticancer therapy.