Title

Homeostasis and the Importance for a Balance Between AKT/mTOR Activity and Intracellular Signaling

Authors

Authors

D. A. Altomare;A. R. Khaled

Comments

Authors: contact us about adding a copy of your work at STARS@ucf.edu

Abbreviated Journal Title

Curr. Med. Chem.

Keywords

Signal transduction; growth factor signaling; tumor progression; metabolism; molecular targeted inhibition; SEVERE INSULIN-RESISTANCE; T-CELL SURVIVAL; GLUCOSE-HOMEOSTASIS; MALIGNANT-TRANSFORMATION; PANCREATIC-CANCER; GENETIC-VARIATION; MAMMALIAN TARGET; MTOR KINASE; DIRECT PHOSPHORYLATION; CALORIE; RESTRICTION; Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology &; Pharmacy

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.

Journal Title

Current Medicinal Chemistry

Volume

19

Issue/Number

22

Publication Date

1-1-2012

Document Type

Review

Language

English

First Page

3748

Last Page

3762

WOS Identifier

WOS:000306494500011

ISSN

0929-8673

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