3-磷酸肌醇依赖性蛋白激酶-1激活AGC家族激酶的机制研究进展

3磷酸肌醇依赖性蛋白激酶1(3phosphoinositidedependentproteinkinase1,PDK1PDPK1)是蛋白激酶B(proteinkinaseB,PKBCAKT)的上游激酶,通过与3,4,5三磷酸磷脂酰肌醇[PtdIns(3,4,5)P3]作用激活相邻的PKB分子.同时,PDK1被称为AGC激酶的掌管者(master),能够激活包含PKB在内的一系列的AGC激酶家族成员.PDK1磷酸化这些激酶的保守区域Tloop区,使它们充分激活,从而调节细胞代谢,生长,扩散,生存,抗凋亡等诸多生理过程.本文就PDK1调节AGC激酶的活性,与功能上命名的PDK2的关系,PDK1分子自身的调节,PH结构域对自身活性及AGC激酶活性的影响,PDK1定位以及作为一个新药物靶标等方面做了综述.

Recent Research Progress on Mechanism of AGC Family Kinases Activated by 3-Phosphoinositide-dependent Protein Kinase-1

3-Phosphoinositide-dependent protein kinase-1(PDK1/PDPK1) is the upstream kinase of protein kinase B (PKB, also known C-AKT), which interacts with PtdIns(3,4,5)P3 and activates neighboring PKB. PDK1 is also termed “the master of AGC kinase". It activates many members of AGC kinase subfamily in addition to PKB. PDK1 phosphorylates the conservative T-loop region of all these AGC members to gain their full activation, which subsequently adjust cellular metabolism ,growth, proliferation, survival, anti-apoptosis and so on. In this article, we summarize recent advances in the studies of PDK1, including how to regulate AGC kinase, relationship between PDK1 and functionally-named PDK2, self-adjustment, how to control PDK1 activation and localization by its PH domain, and particularly, PDK1 as a new drug target, etc.