XB-FEAT-484952

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akt1

This is the community wiki page for the gene akt1 please feel free to add any information that is relevant to this gene that is not already captured elsewhere in Xenbase.

nomenclature changes 13 JULY 2023

Xenopus gene named was updated from v-akt murine thymoma viral oncogene homolog 1 to AKT serine/threonine kinase 1

notes on gene function

Akt, also referred to as PKB or Rac, plays a critical role in controlling survival and apoptosis (1-3). This protein kinase is activated by insulin and various growth and survival factors to function in a wortmannin-sensitive pathway involving PI3 kinase (2,3). Akt is activated by phospholipid binding and activation loop phosphorylation at Thr308 by PDK1 (4) and by phosphorylation within the carboxy terminus at Ser473. The previously elusive PDK2 responsible for phosphorylation of Akt at Ser473 has been identified as mammalian target of rapamycin (mTOR) in a rapamycin-insensitive complex with rictor and Sin1 (5,6). Akt promotes cell survival by inhibiting apoptosis through phosphorylation and inactivation of several targets, including Bad (7), forkhead transcription factors (8), c-Raf (9), and caspase-9. PTEN phosphatase is a major negative regulator of the PI3 kinase/Akt signaling pathway (10). LY294002 is a specific PI3 kinase inhibitor (11). Another essential Akt function is the regulation of glycogen synthesis through phosphorylation and inactivation of GSK-3α and β (12,13). Akt may also play a role in insulin stimulation of glucose transport (12). In addition to its role in survival and glycogen synthesis, Akt is involved in cell cycle regulation by preventing GSK-3β-mediated phosphorylation and degradation of cyclin D1 (14) and by negatively regulating the cyclin dependent kinase inhibitors p27 Kip1 (15) and p21 Waf1/Cip1 (16). Akt also plays a critical role in cell growth by directly phosphorylating mTOR in a rapamycin-sensitive complex containing raptor (17). More importantly, Akt phosphorylates and inactivates tuberin (TSC2), an inhibitor of mTOR within the mTOR-raptor complex (18,19).

references: 1. Franke, T.F. et al. (1997) Cell 88, 435-7. 2. Burgering, B.M. and Coffer, P.J. (1995) Nature 376, 599-602. 3. Franke, T.F. et al. (1995) Cell 81, 727-36. 4. Alessi, D.R. et al. (1996) EMBO J 15, 6541-51. 5. Sarbassov, D.D. et al. (2005) Science 307, 1098-101. 6. Jacinto, E. et al. (2006) Cell 127, 125-37. 7. Cardone, M.H. et al. (1998) Science 282, 1318-21. 8. Brunet, A. et al. (1999) Cell 96, 857-68. 9. Zimmermann, S. and Moelling, K. (1999) Science 286, 1741-4. 10. Cantley, L.C. and Neel, B.G. (1999) Proc Natl Acad Sci USA 96, 4240-5. 11. Vlahos, C.J. et al. (1994) J Biol Chem 269, 5241-8. 12. Hajduch, E. et al. (2001) FEBS Lett 492, 199-203. 13, Cross, D.A. et al. (1995) Nature 378, 785-9. 14. Diehl, J.A. et al. (1998) Genes Dev 12, 3499-511. 15. Gesbert, F. et al. (2000) J Biol Chem 275, 39223-30. 16. Zhou, B.P. et al. (2001) Nat Cell Biol 3, 245-52. 17, Navé, B.T. et al. (1999) Biochem J 344 Pt 2, 427-31. 18. Inoki, K. et al. (2002) Nat Cell Biol 4, 648-57. 19. Manning, B.D. et al. (2002) Mol Cell 10, 151-62.

source: https://www.cellsignal.com/products/primary-antibodies/akt-pan-c67e7-rabbit-mab/4691

summary from NCBi for human AKT1

AKT1 - AKT serine/threonine kinase 1

This gene encodes one of the three members of the human AKT serine-threonine protein kinase family which are often referred to as protein kinase B alpha, beta, and gamma. These highly similar AKT proteins all have an N-terminal pleckstrin homology domain, a serine/threonine-specific kinase domain and a C-terminal regulatory domain. These proteins are phosphorylated by phosphoinositide 3-kinase (PI3K). AKT/PI3K forms a key component of many signalling pathways that involve the binding of membrane-bound ligands such as receptor tyrosine kinases, G-protein coupled receptors, and integrin-linked kinase. These AKT proteins therefore regulate a wide variety of cellular functions including cell proliferation, survival, metabolism, and angiogenesis in both normal and malignant cells. AKT proteins are recruited to the cell membrane by phosphatidylinositol 3,4,5-trisphosphate (PIP3) after phosphorylation of phosphatidylinositol 4,5-bisphosphate (PIP2) by PI3K. Subsequent phosphorylation of both threonine residue 308 and serine residue 473 is required for full activation of the AKT1 protein encoded by this gene. Phosphorylation of additional residues also occurs, for example, in response to insulin growth factor-1 and epidermal growth factor. Protein phosphatases act as negative regulators of AKT proteins by dephosphorylating AKT or PIP3. The PI3K/AKT signalling pathway is crucial for tumor cell survival. Survival factors can suppress apoptosis in a transcription-independent manner by activating AKT1 which then phosphorylates and inactivates components of the apoptotic machinery. AKT proteins also participate in the mammalian target of rapamycin (mTOR) signalling pathway which controls the assembly of the eukaryotic translation initiation factor 4F (eIF4E) complex and this pathway, in addition to responding to extracellular signals from growth factors and cytokines, is disregulated in many cancers. Mutations in this gene are associated with multiple types of cancer and excessive tissue growth including Proteus syndrome and Cowden syndrome 6, and breast, colorectal, and ovarian cancers. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2020]