Authors: A. Altomare, D.; R. Khaled, A.

Source: Current Medicinal Chemistry, Volume 19, Number 22, August 2012 , pp. 3748-3762(15)

Publisher: Bentham Science Publishers

Abstract:

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.

Keywords: Signal transduction; growth factor signaling; tumor progression; metabolism; molecular targeted inhibition

Document Type: Research article

DOI: http://dx.doi.org/10.2174/092986712801661130

Publication date: 2012-08-01

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• Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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