AKT3
RAC-gamma serine/threonine-protein kinase is a protein in humans that is encoded by AKT3 gene. AKT3 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT3 is the least studied AKT isoform. It plays an important role in brain development and is crucial for the viability of malignant glioma cells. AKT3 isoform may also be the key molecule in up-regulation and down-regulation of MMP13 via IL13.
The AKT3 gene directs the generation of RAC-gamma serine/threonine-protein kinase (AKT3), which mediates many processes including metabolism, proliferation, cell survival, growth, and angiogenesis through serine and/or threonine phosphorylation of a range of downstream substrates. The encoding gene of AKT3 produces two almost identical variants via differential splicing of C-terminal exons, making AKT3 distinguishes from the otherwise similar AKT1 and AKT2. AKT3 is a key regulator in the PI3K-AKT-mTOR pathway. Studies have shown that AKT3 is closely associated with the progression of several tumor types especially melanomas, accompanied by widespread PTEN mutations. Downregulated microRNA-217 promotes the occurrence and progression of non-small cell lung cancer (NSCLC) through upregulating AKT3 via the PI3K pathway. By using a powerful clinical molecular diagnostic assay, Matissek KJ et al. identified AKT3 gene fusion and expression is associated with treatment resistance and poor outcome in the hormone receptor-positive breast cancer. AKT3 isoform expression is found in triple-negative breast cancer. AKT3 splice variant lacking serine-472 phosphorylation site promotes apoptosis and suppresses mammary tumorigenesis. Kim M et al. also observed that AKT3 knockdown caused severe structural defects in the mitochondria and an AKT3 deficiency-induced decrease in mitochondrial respiration in A549 lung cancer cells. They concluded that AKT isoforms play distinct roles in mitochondrial function and that AKT3 is critical for proper mitochondrial respiration in human cancer cells.
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