AKT3

AKT3 Full Name

v-akt murine thymoma viral oncogene homolog 3 (protein kinase B, gamma)

AKT3 Introduction

AKT3 is a member of the serine/threonine kinase family of the PI3K–AKT signaling pathway. AKT3 is one of three AKT isoforms that are key regulators of cell survival, growth, and metabolism in many tissues. AKT3 is expressed in high levels in the brain and developing nervous system. High AKT3 expression in these areas indicates the protein plays a role in normal neuronal growth as well as energy balance. Activation and signalling of AKT3 involves phosphorylation that is induced by a number of agents downstream of PI3K. This allows the kinase to relay extracellular signals. AKT3 has a unique expression pattern and regulatory domain structure, indicating distinct biological functions for this kinase that are different from AKT1 and AKT2.

Figure 1. Schematic overview of the AR and PI3K/AKT/mTOR signaling pathways and their crosstalk.(Source: Raith F, et al.; 2023)

On a functional level, AKT3 promotes cellular proliferation, survival, and apoptosis resistance by regulating multiple downstream substrates. In the nervous system, AKT3 has been shown to regulate cortical development, neural stem cell regulation and synapse stabilization. AKT3's effect on metabolic processes maintains energy homeostasis and cellular stress adaptation. AKT3 signaling also has a role in immune cell activation, angiogenesis, and DNA repair.

Clinically, misregulation of AKT3 has been observed in various diseases, especially neurologic disorders and cancer. Variants with loss-of-function have been associated with microcephaly, developmental delay and defects in neuronal growth. Gain-of-function mutations or amplification has also been shown to contribute to tumour progression in several cancer types such as melanoma, glioblastoma, breast cancer and ovarian carcinoma. Dysregulated AKT3 is associated with therapy resistance, uncontrolled growth and metabolic rewiring of cancer cells. AKT3's role in neurodevelopmental disorder and cancer biology suggests AKT3 as a biomarker and a precision medicine therapeutic target.

Alternate Names for AKT3

AKT3; v-akt murine thymoma viral oncogene homolog 3 (protein kinase B, gamma); RAC-gamma serine/threonine-protein kinase; PKBG; PRKBG; RAC gamma; PKB gamma; RAC-gamma serine/threonine protein kinase; STK-2; PKB-GAMMA; RAC-gamma; RAC-PK-gamma; DKFZp434N0250;

• 1. Raith F, et al.; Addressing the Reciprocal Crosstalk between the AR and the PI3K/AKT/mTOR Signaling Pathways for Prostate Cancer Treatment. Int J Mol Sci. 2023, 24(3):2289.