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首页> 外文期刊>Molecular and Cellular Biology >Regulation of Apoptosis by the Ft1 Protein, a New Modulator of Protein Kinase B/Akt
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Regulation of Apoptosis by the Ft1 Protein, a New Modulator of Protein Kinase B/Akt

机译：Ft1蛋白，一种新的蛋白激酶B / Akt调节剂，调节细胞凋亡。

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The serine/threonine kinase protein kinase B (PKB)/Akt plays a central role in many cellular processes, including cell growth, glucose metabolism, and apoptosis. However, the identification and validation of novel regulators or effectors is key to future advances in understanding the multiple functions of PKB. Here we report the identification of a novel PKB binding protein, called Ft1, from a cDNA library screen using a green fluorescent protein-based protein-fragment complementation assay. We show that the Ft1 protein interacts directly with PKB, enhancing the phosphorylation of both of its regulatory sites by promoting its interaction with the upstream kinase PDK1. Further, the modulation of PKB activity by Ft1 has a strong effect on the apoptosis susceptibility of T lymphocytes treated with glucocorticoids. We demonstrate that this phenomenon occurs via a PDK1/PKB/GSK3/NF-ATc signaling cascade that controls the production of the proapoptotic hormone Fas ligand. The wide distribution of Ft1 in adult tissues suggests that it could be a general regulator of PKB activity in the control of differentiation, proliferation, and apoptosis in many cell types.
机译：丝氨酸/苏氨酸激酶蛋白激酶B（PKB）/ Akt在许多细胞过程中起着核心作用，包括细胞生长，葡萄糖代谢和细胞凋亡。但是，识别和验证新型调节剂或效应子是理解PKB多种功能的未来进展的关键。在这里，我们报告使用基于绿色荧光蛋白的蛋白质片段互补测定法从cDNA文库筛选中鉴定出一种新型的PKB结合蛋白，称为Ft1。我们显示Ft1蛋白直接与PKB相互作用，通过促进其与上游激酶PDK1的相互作用来增强其两个调控位点的磷酸化。此外，Ft1对PKB活性的调节对用糖皮质激素治疗的T淋巴细胞的凋亡敏感性有很强的影响。我们证明了这种现象是通过控制促凋亡激素Fas配体的生产的PDK1 / PKB / GSK3 / NF-ATc信号级联发生的。 Ft1在成人组织中的广泛分布表明，它可能是PKB活性在许多细胞类型的分化，增殖和凋亡控制中的一般调节物。

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