Burgering B M, Coffer P J
Laboratory for Physiological Chemistry, Utrecht University, The Netherlands.
Nature. 1995 Aug 17;376(6541):599-602. doi: 10.1038/376599a0.
A serine/threonine kinase, named protein kinase B (PKB) for its sequence homology to both protein kinase A and C, has previously been isolated. PKB, which is identical to the kinase Rac, was later found to be the cellular homologue of the transforming v-Akt. Here we show that PKB is activated by stimuli such as insulin, platelet-derived growth factor (PDGF), epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). Activation of PKB was inhibited by the phosphatidylinositol-3-OH kinase (PI(3)K) inhibitor wortmannin and by coexpression of a dominant-negative mutant of PI(3)K. PDGF receptor mutants that lack detectable associated PI(3)K activity also fail to induce PKB activation, PKB kinase activity is correlated with phosphorylation of PKB on serine. Finally, we show that a constructed Gag-PKB fusion protein, homologous to the v-akt oncogene, displays significantly increased ligand-independent kinase activity. Furthermore, this activity is sufficient to activate the p70 S6-kinase (p70S6K). These results suggest a role for PKB in PI(3)K-mediated signal transduction.
一种丝氨酸/苏氨酸激酶，因其与蛋白激酶A和C的序列同源性而被命名为蛋白激酶B（PKB），此前已被分离出来。后来发现，与激酶Rac相同的PKB是转化型v-Akt的细胞同源物。在这里，我们表明PKB可被胰岛素、血小板衍生生长因子（PDGF）、表皮生长因子（EGF）和碱性成纤维细胞生长因子（bFGF）等刺激物激活。磷脂酰肌醇-3-羟基激酶（PI(3)K）抑制剂渥曼青霉素以及PI(3)K显性负性突变体的共表达可抑制PKB的激活。缺乏可检测到的相关PI(3)K活性的PDGF受体突变体也无法诱导PKB激活，PKB激酶活性与PKB丝氨酸磷酸化相关。最后，我们表明，一种与v-akt癌基因同源的构建的Gag-PKB融合蛋白表现出显著增加的非配体依赖性激酶活性。此外，这种活性足以激活p70 S6激酶（p70S6K）。这些结果表明PKB在PI(3)K介导的信号转导中发挥作用。
