AKT3

== AKT3 ==

AKT3 is a serine/threonine-protein kinase that is encoded by the AKT3 gene in humans. It is a member of the AKT family of kinases, which also includes AKT1 and AKT2. These kinases are critical components of the PI3K/AKT signaling pathway, which is involved in regulating a variety of cellular processes, including metabolism, proliferation, cell survival, growth, and angiogenesis.

Structure

The AKT3 protein, like other members of the AKT family, consists of three main domains:

• The N-terminal pleckstrin homology (PH) domain, which is responsible for binding phosphoinositides and is crucial for membrane localization.
• The central kinase domain, which contains the catalytic activity of the enzyme.
• The C-terminal regulatory domain, which is involved in the regulation of kinase activity.

Function

AKT3 plays a significant role in brain development and function. It is highly expressed in the brain and is involved in the regulation of neuronal survival and growth. AKT3 is also implicated in the regulation of glucose metabolism and has been studied in the context of cancer, where it can contribute to tumorigenesis by promoting cell survival and growth.

Clinical Significance

Mutations and dysregulation of the AKT3 gene have been associated with various disorders. For example, alterations in AKT3 have been linked to:

• Cancer: Overexpression or hyperactivation of AKT3 has been observed in several types of cancer, including glioblastoma, breast cancer, and melanoma. It contributes to oncogenic processes by enhancing cell survival, proliferation, and resistance to apoptosis.
• Neurological Disorders: Mutations in AKT3 have been associated with megalencephaly, a condition characterized by an abnormally large brain. This is due to the role of AKT3 in regulating brain size and neuronal growth.

Research and Therapeutic Implications

Given its role in cancer and neurological disorders, AKT3 is a target of interest for therapeutic intervention. Inhibitors of the PI3K/AKT pathway are being developed and tested in clinical trials for their efficacy in treating cancers with aberrant AKT signaling. Understanding the specific role of AKT3 in these pathways can help in designing targeted therapies that minimize side effects and improve patient outcomes.

References

• Manning BD, Cantley LC. AKT/PKB signaling: navigating downstream. Cell. 2007 Jun 29;129(7):1261-74.
• Vivanco I, Sawyers CL. The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer. 2002 Jul;2(7):489-501.
• Hoxhaj G, Manning BD. The PI3K–AKT network at the interface of oncogenic signalling and cancer metabolism. Nat Rev Cancer. 2020 Jan;20(2):74-88.