Vanhaesebroeck B, Alessi D R
Cell Signalling Group, Ludwig Institute for Cancer Research, 91 Riding House Street, London W1P 8BT, U.K.
Biochem J. 2000 Mar 15;346 Pt 3(Pt 3):561-76.
Phosphoinositide 3-kinases (PI3Ks) generate specific inositol lipids that have been implicated in the regulation of cell growth, proliferation, survival, differentiation and cytoskeletal changes. One of the best characterized targets of PI3K lipid products is the protein kinase Akt or protein kinase B (PKB). In quiescent cells, PKB resides in the cytosol in a low-activity conformation. Upon cellular stimulation, PKB is activated through recruitment to cellular membranes by PI3K lipid products and phosphorylation by 3'-phosphoinositide-dependent kinase-1 (PDK1). Here we review the mechanism by which PKB is activated and the downstream actions of this multifunctional kinase. We also discuss the evidence that PDK1 may be involved in the activation of protein kinases other than PKB, the mechanisms by which this activity of PDK1 could be regulated and the possibility that some of the currently postulated PKB substrates targets might in fact be phosphorylated by PDK1-regulated kinases other than PKB.
磷脂酰肌醇3激酶（PI3Ks）可生成特定的肌醇脂质，这些脂质与细胞生长、增殖、存活、分化及细胞骨架变化的调控有关。PI3K脂质产物最具特征的靶点之一是蛋白激酶Akt或蛋白激酶B（PKB）。在静止细胞中，PKB以低活性构象存在于细胞质中。细胞受到刺激后，PKB通过PI3K脂质产物募集至细胞膜并被3'-磷酸肌醇依赖性激酶-1（PDK1）磷酸化而被激活。在此，我们综述PKB被激活的机制以及这种多功能激酶的下游作用。我们还讨论了PDK1可能参与除PKB之外的蛋白激酶激活的证据、PDK1这种活性可能被调控的机制，以及一些目前假定为PKB底物靶点的蛋白实际上可能被除PKB之外的PDK1调控激酶磷酸化的可能性。
