PKB/Akt: a key mediator of cell proliferation, survival and insulin responses?
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.
Lawlor
M A
MA
MRC Protein Phosphorylation Unit, Department of Life Sciences, University of Dundee, UK.
Alessi
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DR
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D002470:Cell Survival; D003920:Diabetes Mellitus / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction
D007328:Insulin; D011518:Proto-Oncogene Proteins; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt