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COMMENTARY |
MRC Protein Phosphorylation Unit, Department of Life Sciences, University
of Dundee, Dundee DD1 5EH, UK
*
Author for correspondence (e-mail:
d.r.alessi{at}dundee.ac.uk
)
The serine/threonine protein kinase PKB (also known as Akt) is thought to be a key mediator of signal transduction processes. The identification of PKB substrates and the role PKB phosphorylation plays in regulating these molecules have been a major focus of research in recent years. A recently developed motif-profile scoring algorithm that can be used to scan the genome for potential PKB substrates is therefore a useful tool, although additional considerations, such as the evolutionary conservation of the phosphorylation site, must also be taken into account. Recent evidence indicates that PKB plays a key role in cancer progression by stimulating cell proliferation and inhibiting apoptosis and is also probably a key mediator of insulin signalling. These findings indicate that PKB is likely to be a hot drug target for the treatment of cancer, diabetes and stroke. There are, however, a number of pitfalls of methodologies currently employed to study PKB function, and therefore caution should be used in interpretation of such experiments.
Key words: Phosphoinositide 3-kinase, PDK1, AGC kinases, Docking sites, Phospho-specific antibodies, Insulin
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