Regulation of cell size and contractile function by AKT in cardiomyocytes.
AKT is a serine-threonine kinase involved in several different cellular functions, including the control of cell size and the regulation of survival and metabolism. Many studies have demonstrated that AKT also plays a critical role in the homeostasis of the cardiomyocyte. In these cells, AKT is activated by upstream molecules such as beta-adrenergic receptor, insulin-like growth factor-1 or insulin receptor, through PI3K alpha; whereas its activation is inhibited by the PTEN molecule. Downstream targets of AKT in the cardiomyocyte include glycogen-synthase kinase-3 beta and S6 kinase. Major effects of AKT activation in the cardiomyocyte are increase in cell size, prevention of apoptosis, and regulation of glucose metabolism. Interestingly, the AKT-dependent hypertrophic pathway is distinct from that activated by MAPKs. In fact, overexpression of AKT does not lead to MAPK activation. Our group has shown, moreover, that AKT exerts a positive effect on both inotropism and relaxation. In fact, mice overexpressing the E40K mutant of AKT in the heart showed improved cardiac function. Thus, AKT increases both cell size through the S6 kinase pathway and inotropism through the functional regulation of critical Ca(2+)-handling proteins. Therefore, AKT is a critical mediator of physiological hypertrophy.
Latronico
Michael V G
MV
Laboratory of Molecular Cardiology, San Raffaele Biomedical Science Park of Rome, Italy.
Costinean
Stefan
S
Lavitrano
Maria Luisa
ML
Peschle
Cesare
C
Condorelli
Gianluigi
G
D000818:Animals; D048429:Cell Size; D051379:Mice; D008822:Mice, Transgenic; D009200:Myocardial Contraction; D009206:Myocardium / Q000166:cytology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction
D011518:Proto-Oncogene Proteins; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt