AKT
AKT (gene symbol AKT1, also known as protein kinase B alpha, PKB, RAC and RAC-alpha) is a serine/threonine kinase that acts downstream of PI3K. It regulates metabolism, proliferation, cell survival, growth and angiogenesis by phosphorylating a wide range of substrates. Browse Assay Genie's current range of AKT research reagents below, or read on for the biology behind the target.
AKT1 is one of three closely related AKT kinases (AKT1, AKT2 and AKT3) that signal downstream of phosphatidylinositol 3-kinase (PI3K). PI3K converts PIP2 to PIP3, which recruits AKT to the cell membrane. Full activation of AKT1 requires phosphorylation of both Thr-308 and Ser-473. AKT then phosphorylates substrates on serine or threonine residues, and more than 100 candidate substrates have been reported. Growth factors such as PDGF, EGF, insulin and IGF1 all signal through this route. Protein phosphatases act as negative regulators by dephosphorylating AKT or PIP3.
The best-characterised outputs cover several processes. In metabolism, AKT drives insulin-induced translocation of the GLUT4 glucose transporter and inhibits GSK3A and GSK3B to promote glycogen storage. For survival, it phosphorylates MAP3K5 and BAD, and it excludes FOXO transcription factors from the nucleus by promoting 14-3-3 binding. For growth, it phosphorylates TSC2 to activate mTORC1, and it feeds back on mTORC2 through MAPKAP1/SIN1. Further substrates include CREB1, ACLY, PDE3B, RAF1, CDKN1A, MICU1 and METTL1. AKT1 also activates the TMEM175 potassium channel independently of its kinase activity.
The AKT1 gene encodes a protein with an N-terminal pleckstrin homology domain, a kinase domain and a C-terminal regulatory domain. It belongs to the AGC Ser/Thr protein kinase family, RAC subfamily. Its protein is found in the cytoplasm, nucleus, cell membrane and mitochondrial intermembrane space. The gene was originally named v-akt murine thymoma viral oncogene homolog 1, and the protein is also called PRKBA. Multiple transcript variants exist. Mutations in AKT1 are associated with Proteus syndrome, Cowden syndrome 6, and breast, colorectal and ovarian cancers. The PI3K/AKT pathway is crucial for tumour cell survival.
The PI3K/AKT pathway is crucial for tumour cell survival, and AKT1 mutations are associated with breast, colorectal and ovarian cancers.
AKT mediates insulin-induced GLUT4 translocation and glycogen storage through GSK3 phosphorylation, making it central to metabolic signalling studies.
AKT phosphorylates MAP3K5, BAD and FOXO factors, and mediates the antiapoptotic effects of IGF1 in survival pathway research.
AKT phosphorylates TSC2 to activate mTORC1 and feeds back to mTORC2, linking growth factor signals to protein synthesis.
AKT is a serine/threonine kinase activated downstream of PI3K. It phosphorylates many substrates to regulate glucose uptake, glycogen storage, protein synthesis, cell survival, proliferation, growth and angiogenesis, in response to growth factors such as insulin, IGF1, PDGF and EGF.
AKT1 is also called protein kinase B alpha, PKB, PRKBA, RAC and RAC-alpha. Its earlier HGNC name was v-akt murine thymoma viral oncogene homolog 1. The UniProt name is RAC-alpha serine/threonine-protein kinase. Multiple alternatively spliced transcript variants have been reported.
Mouse and rat both have an Akt1 ortholog; check the datasheet of any product for its validated reactivity. AKT1 is one of three human AKT genes (AKT1, AKT2, AKT3). Mutations are associated with Proteus syndrome, Cowden syndrome 6 and several cancers.
Other AKT kinase family members and AKT substrate proteins in the PI3K/AKT/mTOR pathway.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P31749; product specifications from Assay Genie datasheets.