AKT Isoform Activity and Substrate Specificity
Author Information
Author(s): Rachel S. Lee, Colin M. House, Briony E. Cristiano, Ross D. Hannan, Richard B. Pearson, Katherine M. Hannan
Primary Institution: Peter MacCallum Cancer Centre
Hypothesis
Relative tissue/cellular abundance, rather than specific activity, plays the dominant role in determining AKT substrate specificity in situ.
Conclusion
Despite differences in intrinsic activity, the phosphorylation patterns of AKT substrates are largely similar across isoforms in vivo.
Supporting Evidence
- AKT3 is significantly more active than AKT1 in phosphorylating peptide substrates.
- Despite differences in enzyme activity, in vivo substrate specificity is largely similar across AKT isoforms.
- The study utilized both gain- and loss-of-function approaches to assess AKT signaling.
Takeaway
This study shows that how much of each AKT protein is present in a cell is more important than how active each one is when it comes to deciding which jobs they do.
Methodology
The study involved comparing the activity of AKT isoforms in HEK293 cells through gain- and loss-of-function approaches, including siRNA knockdown and overexpression of constitutively active isoforms.
Limitations
The study primarily focused on HEK293 cells, which may not represent all cell types, and the findings may vary in different cellular contexts.
Digital Object Identifier (DOI)
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