Biochemical analysis of Akt 3-specific signal transduction

Akt酶家族由3种蛋白激酶（Akt 1、2和3）组成，并且已显示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。所有这些过程对癌症的生长至关重要。然而，很少有研究区分家庭成员的作用。我们的初步数据显示Akt3比其他两种形式更活跃。此外，使用我们独特的Akt 3特异性抗体，我们发现Akt 3蛋白和活性水平在快速增殖的卵巢癌细胞系和原发性卵巢肿瘤中很高。该提案的目的是阐明通过Akt3的信号传导的模式和作用，包括鉴定靶向底物和信号传导途径以及Akt3驱动的信号传导对细胞特性的影响。这些研究将为了解这个家庭成员在健康和疾病中的作用提供重要线索。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（例如在高表达Akt3的肿瘤如卵巢肿瘤中）打开可能性。从长远来看，将我们的分析研究扩展到其他肿瘤类型将对Akt3作为癌症形成的关键介质的失调程度提供新的见解。

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.