A portrait of AKT kinases: human cancer and animal models depict a family with strong individualities.
More than a decade after their discovery, the three AKT kinase family members have emerged as central players in the signaling cascades that regulate cell growth, proliferation, survival and various aspects of intermediary metabolism. The mechanisms of activation of AKT kinases have been defined in relatively precise terms and new substrates are currently being validated in vivo. However, it is presently unclear whether AKT1, AKT2 and AKT3 are functionally redundant or whether each one performs specific functional role(s). In this review, we will summarize the signaling properties and highlight the specificities of AKT kinases that have emerged from the study of human cancer and animal models. While AKT kinases are an attractive target for pharmacological intervention, knowledge of the precise individual roles of AKT family members will improve the design of highly specific AKT-based therapeutics having reduced toxicity and improved efficacy.
Bellacosa
Alfonso
A
Human Genetics Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA. alfonso.bellacosa@fccc.edu
Testa
Joseph R
JR
Moore
Robert
R
Larue
Lionel
L
D049108:Cell Enlargement; D049109:Cell Proliferation; D002470:Cell Survival; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000503:physiopathology* / Q000628:therapy; D015513:Oncogene Proteins / Q000235:genetics / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction
D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; C494918:AKT1 protein, human; C494921:AKT2 protein, human; C491754:AKT3 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt