PROTEIN-KINASE-B (C-AKT) IN PHOSPHATIDYLINOSITOL-3-OH INASE SIGNAL-TRANSDUCTION
PROTEIN-KINASE-B (C-AKT) IN PHOSPHATIDYLINOSITOL-3-OH INASE SIGNAL-TRANSDUCTION
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DOI：
10.1038/376599a0
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发表时间：
1995-08-17
期刊：
影响因子：
64.8
通讯作者：
COFFER, PJ
中科院分区：
文献类型：
--
作者：
BURGERING, BMT;COFFER, PJ
一种丝氨酸/苏氨酸激酶被命名为蛋白激酶B (PKB)(1)，因为它的序列与蛋白激酶A和C同源。与Rad激酶相同的PKB后来被发现是转化的v-Akt的细胞同源物(3)。本研究表明，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）等刺激激活。磷脂酰肌醇-3- oh激酶（PI(3)K）抑制剂wortmannin和PI(3)K的显性阴性突变体的共表达抑制了PKB的激活。PDGF受体突变体缺乏可检测到的相关PI(3)K活性也不能诱导PKB激活。PKB激酶活性与丝氨酸上PKB的磷酸化有关。最后，我们发现构建的Gag-PKB融合蛋白，与v-akt癌基因同源，显示出显著增加的不依赖配体的激酶活性。此外，这种活性足以激活p70 s6激酶（p70(S6k)）。这些结果表明PKB在PI(3) k介导的信号转导中起作用。
A serine/threonine kinase, named protein kinase B (PKB)(1) for its sequence homology to both protein kinase A and C, has previously been isolated. PKB, which is identical to the kinase Rad, was later found to be the cellular homologue of the transforming v-Akt(3). 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 (p70(S6k)). These results suggest a role for PKB in PI(3)K-mediated signal transduction.