蛋白激酶B及其在磷脂酰肌醇3-激酶介导的信号转导中的作用

Protein Kinase B and Its Role in the Signal Transduction Pathway Mediated by Phosphoinositide 3-Kinase

蛋白激酶B(PKB)是原癌基因c akt的表达产物 ,它参与由生长因子激活的经磷脂酰肌醇 3 激酶 (PI3K)介导的信号转导过程。与许多蛋白激酶相似 ,PKB分子具有一特殊的AH/PH结构域 (AH/PHdomain) ,后者能介导信号分子间的相互作用。PKB是PI3K直接的靶蛋白。PI3K产生的脂类第二信使PI 3,4, P2 和PI 3,4,5 P3等均能与PKB和磷酸肌醇依赖性蛋白激酶 (PDK)的AH/PH结构域结合 ,使二者转位于质膜上并活化。PDK也能使PKB磷酸化而激活 ,激活的PKB又进一步激活抗细胞凋亡机制、葡萄糖代谢 (糖原合成、糖酵解及葡萄糖的摄取 )及蛋白质合成等过程 。

Protein kinase B (PKB) is the expression product of a proto oncongen (c akt), which is involved in the signaling pathways initiated by some growth factors and mediated by phosphoinositide 3 kinase ( PI3K).PKB is a direct target of PI3K. Similar to many protein kinases, PKB has a specific AH/PH domain which can mediate the interaction between signaling molecules. The lipid second messengers, PI 3,4 P 2 and PI 3,4,5 P 3 produced by PI3K, can bind to the AH/PH domain of PKB and of PDK (phosphoinositide dependent protein kinase ). This binding translocates PKB and PDK to the plasma membrane, and activates them. PKB is also activated via phosphorylation by PDK and, in turn, will activate the anti apoptotic machinery, glucose metabolism ( glycogen synthesis, glycolysis and glucose uptake ) and protein synthesis. All these lead to cell growth and proliferation.