Biochemical analysis of Akt 3-specific signal transduction

Akt 3 特异性信号转导的生化分析

• 批准号: nhmrc : 350299
• 负责人: Prof Richard Pearson
• 金额: $ 23.3万
• 依托单位: The University of Melbourne
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2005
• 资助国家: 澳大利亚
• 起止时间: 2005-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/biochemical-analysis-akt-signal-transduction/97587
• 关键词: Biochemical; analysis; Akt; specific; signal

The Akt family of enzymes consists of 3 protein kinases (Akt 1,2 and 3) and has been shown to regulate many normal cellular processes such as cell proliferation, growth, survival and motility, as well as the growth of new blood vessels. All these processes are critical for cancers to grow. However, few studies have distinguished the roles of the individual family members. Our preliminary data revealed Akt3 is far more active than the other two forms. Furthermore, using our unique Akt3 specific antibody, we find Akt 3 protein and activity levels are high in rapidly proliferating ovarian cancer cell lines and in primary ovarian tumours. The aim of this proposal is to characterise the mode and role of signalling via Akt3, including the identification of targeted substrates and signaling pathways and the outcomes of Akt3 driven signaling on cellular properties. These studies will provide important clues to understanding how this family member functions in both health and disease. Elucidation of the basis of Akt3 dependent signalling will open the possibility for the development of drugs that interfere with Akt3 function (for example in high Akt 3 expressing tumours like those of the ovary). In the long term, extension of our profiling studies to other tumour types will give a novel insight into the extent of Akt3 de-regulation as a key mediator of cancer formation.

Akt 酶家族由 3 种蛋白激酶（Akt 1,2 和 3）组成，已被证明可以调节许多正常细胞过程，如细胞增殖、生长、存活和运动，以及新血管的生长。所有这些过程对于癌症的生长都至关重要。然而，很少有研究区分各个家庭成员的角色。我们的初步数据显示 Akt3 比其他两种形式活跃得多。此外，使用我们独特的 Akt3 特异性抗体，我们发现快速增殖的卵巢癌细胞系和原发性卵巢肿瘤中的 Akt 3 蛋白和活性水平很高。该提案的目的是表征 Akt3 信号传导的模式和作用，包括目标底物和信号传导途径的识别以及 Akt3 驱动的信号传导对细胞特性的影响。这些研究将为了解该家庭成员在健康和疾病方面的功能提供重要线索。阐明 Akt3 依赖性信号传导的基础将为开发干扰 Akt3 功能的药物提供可能性（例如在高 Akt 3 表达的肿瘤中，如卵巢肿瘤）。从长远来看，将我们的分析研究扩展到其他肿瘤类型将为 Akt3 失调作为癌症形成关键介质的程度提供新的见解。