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Regulation of Cell Size and Contractile Function by AKT in Cardiomyocytes
Author(s) -
LATRONICO MICHAEL V. G.,
COSTINEAN STEFAN,
LAVITRANO MARIA LUISA,
PESCHLE CESARE,
CONDORELLI GIANLUIGI
Publication year - 2004
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1302.021
Subject(s) - protein kinase b , microbiology and biotechnology , function (biology) , cell function , chemistry , cell , signal transduction , biology , biochemistry
A bstract : 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 β‐adrenergic receptor, insulin‐like growth factor‐1 or insulin receptor, through PI3Kα; whereas its activation is inhibited by the PTEN molecule. Downstream targets of AKT in the cardiomyocyte include glycogen‐synthase kinase‐3β 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.