AKT2, also known as protein kinase Bβ (PKBβ), is a key serine/threonine-specific protein kinase involved in various cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription, and cell migration. It is ubiquitously expressed but is most prominently found in tissues with extensive metabolic activity, such as liver, muscle, and adipose tissue. Activation of AKT2 occurs primarily through the PI3K/AKT signaling pathway. When extracellular signals stimulate receptors, phosphoinositide 3-kinase (PI3K) is activated, which subsequently phosphorylates the lipid phosphatidylinositol (4,5)-bisphosphate (PIP2) to phosphatidylinositol (3,4,5)-triphosphate (PIP3). PIP3 then recruits AKT2 to the plasma membrane, where it undergoes a conformational change and becomes phosphorylated at two key residues, Thr309 and Ser474, to become fully activated.
Mutations and dysregulation of AKT2 are associated with a variety of diseases, especially metabolic disorders such as type 2 diabetes. For example, gain-of-function mutations in AKT2 can lead to severe hypoglycemia due to uncontrolled activation of the insulin signaling pathway. Conversely, loss-of-function mutations are associated with insulin resistance and diabetes due to impaired glucose transport. In cancer biology, AKT2 overexpression and overactivation are common in various cancers, including breast, ovarian, and pancreatic cancers. Its role in promoting cell survival, growth, and proliferation makes AKT2 an important therapeutic target in oncology.
The human AKT2 knockout cell line - HCT116 is a powerful research tool that can be used in a variety of biological and medical studies. Here are some of the key applications of this particular cell line:
Cancer Research: AKT2 is known to play a crucial role in cancer progression and metastasis. Utilizing the AKT2 knockout HCT116 cell line, researchers can study the specific role of AKT2 in tumorigenesis, including cell proliferation, survival, and migration.
Signal Transduction Studies: AKT2 is a key player in various signaling pathways, including the PI3K/AKT pathway involved in regulating cell growth and metabolism. By studying the AKT2 knockout cell line, scientists can dissect complex signaling networks and understand how the loss of AKT2 affects various downstream targets and cellular processes.
Drug Screening and Development: This cell line can be used in high-throughput screening assays to identify and evaluate the efficacy of new drugs targeting the AKT2 pathway. It can be used as a preclinical model to test how drugs affect cells lacking AKT2, helping to identify potential therapeutic agents for diseases associated with AKT2.
Metabolic Studies: AKT2 plays an important role in cellular metabolism, including glucose uptake and lipid metabolism. Researchers can use the AKT2 knockout HCT116 cell line to study metabolic disorders, such as diabetes and obesity.
Genomic and Proteomic Analysis: By performing genomic and proteomic analysis on the AKT2 knockout cell line, scientists can identify changes in gene expression and protein interaction networks that are altered due to the loss of AKT2.