Table of Contents Author Guidelines Submit a Manuscript
Enzyme Research
Volume 2011, Article ID 720985, 18 pages
Research Article

Relative Expression Levels Rather Than Specific Activity Plays the Major Role in Determining In Vivo AKT Isoform Substrate Specificity

1Growth Control and Differentiation Program, Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, Melbourne, VIC 8006, Australia
2Cancer Genomics Genetics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC 8006, Australia
3Cephalon Australia Pty Ltd., Parkville, VIC 3052, Australia
4Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, VIC 3010, Australia
5Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3168, Australia

Received 7 March 2011; Revised 8 June 2011; Accepted 9 June 2011

Academic Editor: Heung Chin Cheng

Copyright © 2011 Rachel S. Lee et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.