Lee Rachel S, House Colin M, Cristiano Briony E, Hannan Ross D, Pearson Richard B, Hannan Katherine M
Growth Control and Differentiation Program, Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, Melbourne, VIC 8006, Australia.
Enzyme Res. 2011;2011:720985. doi: 10.4061/2011/720985. Epub 2011 Aug 22.
The AKT protooncogene mediates many cellular processes involved in normal development and disease states such as cancer. The three structurally similar isoforms: AKT1, AKT2, and AKT3 exhibit both functional redundancy and isoform-specific functions; however the basis for their differential signalling remains unclear. Here we show that in vitro, purified AKT3 is ∼47-fold more active than AKT1 at phosphorylating peptide and protein substrates. Despite these marked variations in specific activity between the individual isoforms, a comprehensive analysis of phosphorylation of validated AKT substrates indicated only subtle differences in signalling via individual isoforms in vivo. Therefore, we hypothesise, at least in this model system, that relative tissue/cellular abundance, rather than specific activity, plays the dominant role in determining AKT substrate specificity in situ.
AKT原癌基因介导许多参与正常发育和疾病状态（如癌症）的细胞过程。三种结构相似的亚型：AKT1、AKT2和AKT3既表现出功能冗余，也具有亚型特异性功能；然而，它们差异信号传导的基础仍不清楚。在这里，我们表明在体外，纯化的AKT3在磷酸化肽和蛋白质底物方面的活性比AKT1高约47倍。尽管各个亚型之间的比活性存在显著差异，但对经过验证的AKT底物磷酸化的全面分析表明，体内通过各个亚型的信号传导仅存在细微差异。因此，我们推测，至少在这个模型系统中，相对组织/细胞丰度而非比活性在原位确定AKT底物特异性方面起主导作用。
