It has been suggested that portions of Protein kinase B be split from it and merged into this article. (Discuss) (September 2017)
RAC(Rho family)-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) protein domains.[5] It is commonly referred to as PKB, or by both names as "Akt/PKB".
The serine-threonine protein kinase AKT1 is catalytically inactive in serum-starved primary and immortalized fibroblasts. AKT1 and the related AKT2 are activated by platelet-derived growth factor. The activation is rapid and specific, and it is abrogated by mutations in the pleckstrin homology domain of AKT1. It was shown that the activation occurs through phosphatidylinositol 3-kinase. In the developing nervous system AKT is a critical mediator of growth factor-induced neuronal survival. Survival factors can suppress apoptosis in a transcription-independent manner by activating the serine/threonine kinase AKT1, which then phosphorylates and inactivates components of the apoptotic machinery. Mice lacking Akt1 display a 25% reduction in body mass, indicating that Akt1 is critical for transmitting growth-promoting signals, most likely via the IGF1 receptor. Mice lacking Akt1 are also resistant to cancer: They experience considerable delay in tumor growth initiated by the large T antigen or the Neu oncogene. A single-nucleotide polymorphism in this gene causes Proteus syndrome.[6][7]
Historyedit
AKT (now also called AKT1) was originally identified as the oncogene in the transforming retrovirus, AKT8.[8] 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.[9]
In 2011, a mutation in AKT1 was strongly associated with Proteus syndrome, the disease that probably affected the Elephant Man.[10]
The name Akt stands for Ak strain transforming. The origins of the Akt name date back to 1928, when 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.
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^Staal SP (July 1987). "Molecular cloning of the akt oncogene and its human homologues AKT1 and AKT2: amplification of AKT1 in a primary human gastric adenocarcinoma". Proc. Natl. Acad. Sci. U.S.A. 84 (14): 5034–7. Bibcode:1987PNAS...84.5034S. doi:10.1073/pnas.84.14.5034. PMC305241. PMID 3037531.
^Lindhurst MJ, Sapp JC, Teer JK, Johnston JJ, Finn EM, Peters K, Turner J, Cannons JL, Bick D, Blakemore L, Blumhorst C, Brockmann K, Calder P, Cherman N, Deardorff MA, Everman DB, Golas G, Greenstein RM, Kato BM, Keppler-Noreuil KM, Kuznetsov SA, Miyamoto RT, Newman K, Ng D, O'Brien K, Rothenberg S, Schwartzentruber DJ, Singhal V, Tirabosco R, Upton J, Wientroub S, Zackai EH, Hoag K, Whitewood-Neal T, Robey PG, Schwartzberg PL, Darling TN, Tosi LL, Mullikin JC, Biesecker LG (27 July 2011). "A Mosaic Activating Mutation in Associated with the Proteus Syndrome". New England Journal of Medicine. 365 (7): 611–619. doi:10.1056/NEJMoa1104017. PMC3170413. PMID 21793738.
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^Delcommenne M, Tan C, Gray V, Rue L, Woodgett J, Dedhar S (Sep 1998). "Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase". Proc. Natl. Acad. Sci. U.S.A. 95 (19): 11211–6. Bibcode:1998PNAS...9511211D. doi:10.1073/pnas.95.19.11211. PMC21621. PMID 9736715.
^Paramio JM, Segrelles C, Ruiz S, Jorcano JL (Nov 2001). "Inhibition of protein kinase B (PKB) and PKCzeta mediates keratin K10-induced cell cycle arrest". Mol. Cell. Biol. 21 (21): 7449–59. doi:10.1128/MCB.21.21.7449-7459.2001. PMC99917. PMID 11585925.
^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. PMID 11707464.
^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. PMID 12458207.
^ abRane MJ, Coxon PY, Powell DW, Webster R, Klein JB, Pierce W, Ping P, McLeish KR (Feb 2001). "p38 Kinase-dependent MAPKAPK-2 activation functions as 3-phosphoinositide-dependent kinase-2 for Akt in human neutrophils". J. Biol. Chem. 276 (5): 3517–23. doi:10.1074/jbc.M005953200. PMID 11042204.
^Dickey CA, Koren J, Zhang YJ, Xu YF, Jinwal UK, Birnbaum MJ, Monks B, Sun M, Cheng JQ, Patterson C, Bailey RM, Dunmore J, Soresh S, Leon C, Morgan D, Petrucelli L (Mar 2008). "Akt and CHIP coregulate tau degradation through coordinated interactions". Proc. Natl. Acad. Sci. U.S.A. 105 (9): 3622–7. Bibcode:2008PNAS..105.3622D. doi:10.1073/pnas.0709180105. PMC2265134. PMID 18292230.
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^ abLaine J, Künstle G, Obata T, Sha M, Noguchi M (Aug 2000). "The protooncogene TCL1 is an Akt kinase coactivator". Mol. Cell. 6 (2): 395–407. doi:10.1016/S1097-2765(00)00039-3. PMID 10983986.
^Sarbassov DD, Guertin DA, Ali SM, Sabatini DM (Feb 2005). "Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex". Science. 307 (5712): 1098–101. Bibcode:2005Sci...307.1098S. doi:10.1126/science.1106148. PMID 15718470. S2CID 45837814.
^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. PMID 10910062.
^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. PMID 14970221.
^Lee SB, Xuan Nguyen TL, Choi JW, Lee KH, Cho SW, Liu Z, Ye K, Bae SS, Ahn JY (Oct 2008). "Nuclear Akt interacts with B23/NPM and protects it from proteolytic cleavage, enhancing cell survival". Proc. Natl. Acad. Sci. U.S.A. 105 (43): 16584–9. Bibcode:2008PNAS..10516584L. doi:10.1073/pnas.0807668105. PMC2569968. PMID 18931307.
^Pekarsky Y, Hallas C, Palamarchuk A, Koval A, Bullrich F, Hirata Y, Bichi R, Letofsky J, Croce CM (Mar 2001). "Akt phosphorylates and regulates the orphan nuclear receptor Nur77". Proc. Natl. Acad. Sci. U.S.A. 98 (7): 3690–4. Bibcode:2001PNAS...98.3690P. doi:10.1073/pnas.051003198. PMC31113. PMID 11274386.
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Further readingedit
Hemmings BA (1997). "Akt signaling: linking membrane events to life and death decisions". Science. 275 (5300): 628–30. doi:10.1126/science.275.5300.628. PMID 9019819. S2CID 5224712.
Vanhaesebroeck B, Alessi DR (2000). "The PI3K-PDK1 connection: more than just a road to PKB". Biochem. J. 346 (3): 561–76. doi:10.1042/0264-6021:3460561. PMC1220886. PMID 10698680.
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. PMID 10872470.
Pekarsky Y, Hallas C, Croce CM (2001). "Molecular basis of mature T-cell leukemia". JAMA. 286 (18): 2308–14. doi:10.1001/jama.286.18.2308. PMID 11710897.
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. PMID 15271644. S2CID 25834366.
Manning BD (2004). "Balancing Akt with S6K: implications for both metabolic diseases and tumorigenesis". J. Cell Biol. 167 (3): 399–403. doi:10.1083/jcb.200408161. PMC2172491. PMID 15533996.
Shinohara M, Chung YJ, Saji M, Ringel MD (2007). "AKT in thyroid tumorigenesis and progression". Endocrinology. 148 (3): 942–7. doi:10.1210/en.2006-0937. PMID 16946008.
External linksedit
AKT1 Standards - Learn more about AKT1 Reference Controls
Human AKT1 genome location and AKT1 gene details page in the UCSC Genome Browser.