The PI 3-kinase/Akt signaling pathway delivers an anti-apoptotic signal
The PI 3-kinase/Akt signaling pathway delivers an anti-apoptotic signal
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DOI：
10.1101/gad.11.6.701
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发表时间：
1997-03-15
影响因子：
10.5
通讯作者：
Hay, N
中科院分区：
文献类型：
--
作者：
Kennedy, SG;Wagner, AJ;Hay, N
血清和某些生长因子具有抑制程序性细胞死亡（凋亡）和促进存活的能力。生长因子传递抗凋亡信号的机制和这种存活信号与有丝分裂发生解偶联的机制尚不清楚。我们研究了生长因子受体的五种下游效应物Ras、Raf、Src、磷酸肌醇3-激酶（PI 3-kinase）和Akt（PKB）阻断细胞凋亡的能力。激活形式的Pas，Raf，和Src，虽然转化，不足以提供一个生存信号后血清撤出。相反，PI 3-激酶的抑制加速细胞凋亡，并且PI 3-激酶的下游效应物丝氨酸/苏氨酸激酶Akt的活化形式阻断细胞凋亡。Akt促进存活的能力依赖于其激酶活性并与其成比例。在Rat 1a成纤维细胞中，激活的Akt不改变Bcl-2或Bcl-X（L）的表达，但抑制Ced 3/ICE样活性。因此，PI 5-激酶/Akt（PKB）信号传导途径转导最终阻断Ced 3/ICE样活性的存活信号。这些结果表明，解偶联的生存和有丝分裂可以解释不同的有丝分裂原的能力，有效地诱导PI 3-激酶/Akt信号通路。
Serum and certain growth factors have the ability to inhibit programmed cell death (apoptosis) and promote survival. The mechanism by which growth factors deliver an anti-apoptotic signal and the mechanism by which this survival signal is uncoupled from mitogenesis are not clear. We studied five downstream effectors of growth factor receptors-Ras, Raf, Src, phosphoinositide 3-kinase (PI 3-kinase), and Akt (PKB)-for their abilities to block apoptosis. Activated forms of Pas, Raf, and Src, although transforming, were not sufficient to deliver a survival signal upon serum withdrawal. In contrast, inhibition of PI S-kinase accelerated apoptosis, and an activated form of the serine/threonine kinase Akt, a downstream effector of PI 3-kinase, blocked apoptosis. The ability of Akt to promote survival was dependent on and proportional to its kinase activity. In Rat1a fibroblasts, activated Akt did not alter Bcl-2 or Bcl-X(L), expression but inhibited Ced3/ICE-like activity. Thus, the PI 5-kinase/Akt (PKB) signaling pathway transduces a survival signal that ultimately blocks Ced3/ICE-like activity. These results suggest that uncoupling of survival and mitogenesis can be explained by differing abilities of distinct mitogens to efficiently induce the PI 3-kinase/Akt signaling pathway.