RAC-alpha serine/threonine-protein kinase is an enzyme that in humans is encoded by the AKT1gene. This enzyme belongs to the AKT subfamily of serine/threonine kinases that contain SH2 (Src homology 2-like) domains. It is commonly referred to as PKB, or by both names as "Akt/PKB".
AKT (now also called AKT1) was originally identified as the oncogene in the transforming retrovirus, AKT8. AKT8 was isolated from a spontaneous thymoma cell line derived from AKR mice by cocultivation with an indicator mink cell line. The transforming cellular sequences, v-akt, were cloned from a transformed mink cell clone and these sequences were used to identify Akt1 and Akt2 in a human clone library. AKT8 was isolated by Stephen Staal in the laboratory of Wallace P. Rowe; he subsequently cloned v-akt and human AKT1 and AKT2 while on staff at the Johns Hopkins Oncology Center.
In 2011, a mutation in AKT1 was strongly associated with Proteus syndrome, the disease that probably affected the Elephant Man.
The name Akt stands for Ak strain transforming. The origins of the Akt name date back to 1928, where J. Furth performed experimental studies on mice that developed spontaneous thymic lymphomas. Mice from three different stocks were studied, and the stocks were designated A, R, and S. Stock A was noted to yield many cancers, and inbred families were subsequently designated by a second small letter (Aa, Ab, Ac, etc.), and thus came the Ak strain of mice. Further inbreeding was undertaken with Ak mice at the Rockefeller Institute in 1936, leading to the designation of the AKR mouse strain. In 1977, a transforming retrovirus was isolated from the AKR mouse. This virus was named Akt-8, the "t" representing its transforming capabilities.
^Guan KL, Figueroa C, Brtva TR, Zhu T, Taylor J, Barber TD, Vojtek AB (Sep 2000). "Negative regulation of the serine/threonine kinase B-Raf by Akt". J. Biol. Chem.275 (35): 27354–9. doi:10.1074/jbc.M004371200. PMID10869359.
^Altiok S, Batt D, Altiok N, Papautsky A, Downward J, Roberts TM, Avraham H (Nov 1999). "Heregulin induces phosphorylation of BRCA1 through phosphatidylinositol 3-Kinase/AKT in breast cancer cells". J. Biol. Chem.274 (45): 32274–8. doi:10.1074/jbc.274.45.32274. PMID10542266.
^Fujita N, Sato S, Katayama K, Tsuruo T (Aug 2002). "Akt-dependent phosphorylation of p27Kip1 promotes binding to 14-3-3 and cytoplasmic localization". J. Biol. Chem.277 (32): 28706–13. doi:10.1074/jbc.M203668200. PMID12042314.
^Ozes ON, Mayo LD, Gustin JA, Pfeffer SR, Pfeffer LM, Donner DB (Sep 1999). "NF-kappaB activation by tumour necrosis factor requires the Akt serine-threonine kinase". Nature401 (6748): 82–5. doi:10.1038/43466. PMID10485710.
^Romashkova JA, Makarov SS (Sep 1999). "NF-kappaB is a target of AKT in anti-apoptotic PDGF signalling". Nature401 (6748): 86–90. doi:10.1038/43474. PMID10485711.
^Haendeler J, Hoffmann J, Rahman S, Zeiher AM, Dimmeler S (Feb 2003). "Regulation of telomerase activity and anti-apoptotic function by protein-protein interaction and phosphorylation". FEBS Lett.536 (1-3): 180–6. doi:10.1016/s0014-5793(03)00058-9. PMID12586360.
^Kawauchi K, Ihjima K, Yamada O (May 2005). "IL-2 increases human telomerase reverse transcriptase activity transcriptionally and posttranslationally through phosphatidylinositol 3'-kinase/Akt, heat shock protein 90, and mammalian target of rapamycin in transformed NK cells". J. Immunol.174 (9): 5261–9. doi:10.4049/jimmunol.174.9.5261. PMID15843522.
^ abBarry FA, Gibbins JM (Apr 2002). "Protein kinase B is regulated in platelets by the collagen receptor glycoprotein VI". J. Biol. Chem.277 (15): 12874–8. doi:10.1074/jbc.M200482200. PMID11825911.
^ abPersad S, Attwell S, Gray V, Mawji N, Deng JT, Leung D, Yan J, Sanghera J, Walsh MP, Dedhar S (Jul 2001). "Regulation of protein kinase B/Akt-serine 473 phosphorylation by integrin-linked kinase: critical roles for kinase activity and amino acids arginine 211 and serine 343". J. Biol. Chem.276 (29): 27462–9. doi:10.1074/jbc.M102940200. PMID11313365.
^Park HS, Kim MS, Huh SH, Park J, Chung J, Kang SS, Choi EJ (Jan 2002). "Akt (protein kinase B) negatively regulates SEK1 by means of protein phosphorylation". J. Biol. Chem.277 (4): 2573–8. doi:10.1074/jbc.M110299200. PMID11707464.
^Barthwal MK, Sathyanarayana P, Kundu CN, Rana B, Pradeep A, Sharma C, Woodgett JR, Rana A (Feb 2003). "Negative regulation of mixed lineage kinase 3 by protein kinase B/AKT leads to cell survival". J. Biol. Chem.278 (6): 3897–902. doi:10.1074/jbc.M211598200. PMID12458207.
^ abLaine J, Künstle G, Obata T, Noguchi M (Feb 2002). "Differential regulation of Akt kinase isoforms by the members of the TCL1 oncogene family". J. Biol. Chem.277 (5): 3743–51. doi:10.1074/jbc.M107069200. PMID11707444.
^Sarbassov DD, Guertin DA, Ali SM, Sabatini DM (Feb 2005). "Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex". Science307 (5712): 1098–101. doi:10.1126/science.1106148. PMID15718470.
^Sekulić A, Hudson CC, Homme JL, Yin P, Otterness DM, Karnitz LM, Abraham RT (Jul 2000). "A direct linkage between the phosphoinositide 3-kinase-AKT signaling pathway and the mammalian target of rapamycin in mitogen-stimulated and transformed cells". Cancer Res.60 (13): 3504–13. PMID10910062.
^Cheng SW, Fryer LG, Carling D, Shepherd PR (Apr 2004). "Thr2446 is a novel mammalian target of rapamycin (mTOR) phosphorylation site regulated by nutrient status". J. Biol. Chem.279 (16): 15719–22. doi:10.1074/jbc.C300534200. PMID14970221.
^Koh H, Lee KH, Kim D, Kim S, Kim JW, Chung J (Nov 2000). "Inhibition of Akt and its anti-apoptotic activities by tumor necrosis factor-induced protein kinase C-related kinase 2 (PRK2) cleavage". J. Biol. Chem.275 (44): 34451–8. doi:10.1074/jbc.M001753200. PMID10926925.
^Bauer B, Krumböck N, Fresser F, Hochholdinger F, Spitaler M, Simm A, Uberall F, Schraven B, Baier G (Aug 2001). "Complex formation and cooperation of protein kinase C theta and Akt1/protein kinase B alpha in the NF-kappa B transactivation cascade in Jurkat T cells". J. Biol. Chem.276 (34): 31627–34. doi:10.1074/jbc.M103098200. PMID11410591.
^French SW, Shen RR, Koh PJ, Malone CS, Mallick P, Teitell MA (May 2002). "A modeled hydrophobic domain on the TCL1 oncoprotein mediates association with AKT at the cytoplasmic membrane". Biochemistry41 (20): 6376–82. doi:10.1021/bi016068o. PMID12009899.
^Du K, Herzig S, Kulkarni RN, Montminy M (Jun 2003). "TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in liver". Science300 (5625): 1574–7. doi:10.1126/science.1079817. PMID12791994.
^ abDan HC, Sun M, Yang L, Feldman RI, Sui XM, Ou CC, Nellist M, Yeung RS, Halley DJ, Nicosia SV, Pledger WJ, Cheng JQ (Sep 2002). "Phosphatidylinositol 3-kinase/Akt pathway regulates tuberous sclerosis tumor suppressor complex by phosphorylation of tuberin". J. Biol. Chem.277 (38): 35364–70. doi:10.1074/jbc.M205838200. PMID12167664.
^Powell DW, Rane MJ, Chen Q, Singh S, McLeish KR (Jun 2002). "Identification of 14-3-3zeta as a protein kinase B/Akt substrate". J. Biol. Chem.277 (24): 21639–42. doi:10.1074/jbc.M203167200. PMID11956222.
Chan TO, Rittenhouse SE, Tsichlis PN (2000). "AKT/PKB and other D3 phosphoinositide-regulated kinases: kinase activation by phosphoinositide-dependent phosphorylation". Annu. Rev. Biochem.68: 965–1014. doi:10.1146/annurev.biochem.68.1.965. PMID10872470.
Dickson LM, Rhodes CJ (2004). "Pancreatic beta-cell growth and survival in the onset of type 2 diabetes: a role for protein kinase B in the Akt?". Am. J. Physiol. Endocrinol. Metab.287 (2): E192–8. doi:10.1152/ajpendo.00031.2004. PMID15271644.