Homeostasis and the Importance for a Balance Between AKT/mTOR Activity and Intracellular Signaling
D. A. Altomare and A. R. Khaled
Pages 3748-3762 (15)
The AKT family of serine threonine kinases is of critical importance with regard to growth factor signaling, cell proliferation,
survival and oncogenesis. Engagement of signaling receptors induces the lipid kinase, phosphatidylinositol 3-kinase (PI3K), which
enables the activation of AKT. Responsive to the PI3K/AKT pathway is the mammalian target of rapamycin (mTOR), a major effector
that is specifically implicated in the regulation of cell growth as a result of nutrient availability and cellular bioenergetics. These kinases
mediate the activity of a multitude of intracellular signaling molecules and intersect with multiple pathways that regulate cellular
processes. Elucidating the role of AKT/mTOR in metabolism and in hallmark signaling pathways that are aberrantly affected in cancer
has provided a solid foundation of discoveries. From this, new research directions are emerging with regard to the role of AKT/mTOR in
diabetes and T cell-mediated immunity. As a result, a new perspective is developing in how AKT/mTOR functions within intracellular
signaling pathways to maintain cellular homeostasis. An appreciation is emerging that altered equilibrium of AKT/mTOR pathways
contributes to disease and malignancy. Such new insights may lead to novel intervention strategies that may be useful to reprogram or
reset the balance of intracellular signaling.
Signal transduction, growth factor signaling, tumor progression, metabolism, molecular targeted inhibition
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, 6900 Lake Nona Blvd., Orlando, FL 32827, USA.