AKT2

= AKT2 =

AKT2, also known as RAC-beta serine/threonine-protein kinase, is a protein that in humans is encoded by the AKT2 gene. It is a member of the AKT family of serine/threonine-specific protein kinases, which are involved in various cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription, and cell migration.

Structure

The AKT2 protein is composed of 481 amino acids and has a molecular weight of approximately 56 kDa. It contains three important domains:

• Pleckstrin Homology (PH) Domain: This domain is responsible for binding phosphoinositides, which are important for the recruitment of AKT2 to the plasma membrane.
• Kinase Domain: This domain is responsible for the catalytic activity of the protein, phosphorylating serine and threonine residues on substrate proteins.
• Regulatory Domain: This domain contains sites for phosphorylation that regulate the activity of AKT2.

Function

AKT2 plays a critical role in the insulin signaling pathway. It is activated by phosphorylation in response to insulin and other growth factors. Once activated, AKT2 phosphorylates a variety of substrates involved in glucose uptake, glycogen synthesis, and lipid metabolism.

Role in Glucose Metabolism

AKT2 is particularly important in the regulation of glucose metabolism. It facilitates the translocation of glucose transporter 4 (GLUT4) to the cell membrane, thereby increasing glucose uptake in response to insulin.

Role in Cell Survival and Growth

AKT2 promotes cell survival by inhibiting apoptotic pathways. It phosphorylates and inactivates components of the apoptotic machinery, such as BAD and caspase-9, thereby preventing cell death.

Clinical Significance

Mutations and dysregulation of AKT2 have been implicated in various diseases, including cancer and diabetes.

Cancer

AKT2 is often overexpressed or hyperactivated in several types of cancer, including ovarian, breast, and pancreatic cancers. Its role in promoting cell survival and growth makes it a potential target for cancer therapy.

Diabetes

Mutations in the AKT2 gene can lead to insulin resistance and type 2 diabetes. A specific mutation, AKT2 E17K, has been associated with severe insulin resistance and diabetes.

Therapeutic Target

Given its role in cancer and metabolic diseases, AKT2 is a target for drug development. Inhibitors of AKT2 are being investigated for their potential to treat cancer and metabolic disorders.

References

• Bellacosa, A., et al. (1991). "Molecular cloning of Akt2, a member of the Akt/PKB subfamily of serine/threonine kinases with oncogenic potential." Proc Natl Acad Sci U S A. 88(23): 10424–10428.
• Altomare, D. A., & Testa, J. R. (2005). "Perturbations of the AKT signaling pathway in human cancer." Oncogene. 24(50): 7455–7464.
• George, S., et al. (2004). "A family with severe insulin resistance and diabetes due to a mutation in AKT2." Science. 304(5675): 1325–1328.

External Links

• [AKT2 Gene - GeneCards](https://www.genecards.org/cgi-bin/carddisp.pl?gene=AKT2)
• [AKT2 Protein - UniProt](https://www.uniprot.org/uniprot/P31751)