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{{Infobox_gene}}
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'''V-akt murine thymoma viral oncogene homolog 1''', also known as '''AKT1''', is a human [[gene]].
<!-- This infobox is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{GNF_Protein_box
| image = PBB_Protein_AKT1_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1h10.
| PDB = {{PDB2|1h10}}, {{PDB2|1unp}}, {{PDB2|1unq}}, {{PDB2|1unr}}, {{PDB2|2uvm}}
| Name = V-akt murine thymoma viral oncogene homolog 1
| HGNCid = 391
| Symbol = AKT1
| AltSymbols =; AKT; MGC99656; PKB; PRKBA; RAC; RAC-ALPHA
| OMIM = 164730
| ECnumber = 
| Homologene = 3785
| MGIid = 87986
| GeneAtlas_image1 = PBB_GE_AKT1_207163_s_at.png
<!-- The Following entry is a time stamp of the last bot update.  It is typically hidden data -->
| DateOfBotUpdate = 17:21, 11 September 2007 (UTC)
| Function = {{GNF_GO|id=GO:0000166 |text = nucleotide binding}} {{GNF_GO|id=GO:0004672 |text = protein kinase activity}} {{GNF_GO|id=GO:0004674 |text = protein serine/threonine kinase activity}} {{GNF_GO|id=GO:0005351 |text = sugar:hydrogen ion symporter activity}} {{GNF_GO|id=GO:0005524 |text = ATP binding}} {{GNF_GO|id=GO:0016740 |text = transferase activity}} {{GNF_GO|id=GO:0042802 |text = identical protein binding}}  
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005737 |text = cytoplasm}} {{GNF_GO|id=GO:0005819 |text = spindle}} {{GNF_GO|id=GO:0030027 |text = lamellipodium}}
| Process = {{GNF_GO|id=GO:0000060 |text = protein import into nucleus, translocation}} {{GNF_GO|id=GO:0005975 |text = carbohydrate metabolic process}} {{GNF_GO|id=GO:0005978 |text = glycogen biosynthetic process}} {{GNF_GO|id=GO:0006006 |text = glucose metabolic process}} {{GNF_GO|id=GO:0006417 |text = regulation of translation}} {{GNF_GO|id=GO:0006468 |text = protein amino acid phosphorylation}} {{GNF_GO|id=GO:0006809 |text = nitric oxide biosynthetic process}} {{GNF_GO|id=GO:0006810 |text = transport}} {{GNF_GO|id=GO:0006915 |text = apoptosis}} {{GNF_GO|id=GO:0006954 |text = inflammatory response}} {{GNF_GO|id=GO:0007165 |text = signal transduction}} {{GNF_GO|id=GO:0007186 |text = G-protein coupled receptor protein signaling pathway}} {{GNF_GO|id=GO:0007281 |text = germ cell development}} {{GNF_GO|id=GO:0008286 |text = insulin receptor signaling pathway}} {{GNF_GO|id=GO:0008637 |text = apoptotic mitochondrial changes}} {{GNF_GO|id=GO:0009408 |text = response to heat}} {{GNF_GO|id=GO:0009725 |text = response to hormone stimulus}} {{GNF_GO|id=GO:0015758 |text = glucose transport}} {{GNF_GO|id=GO:0016567 |text = protein ubiquitination}} {{GNF_GO|id=GO:0030163 |text = protein catabolic process}} {{GNF_GO|id=GO:0042640 |text = anagen}} {{GNF_GO|id=GO:0045884 |text = regulation of survival gene product activity}} {{GNF_GO|id=GO:0046777 |text = protein amino acid autophosphorylation}} {{GNF_GO|id=GO:0048009 |text = insulin-like growth factor receptor signaling pathway}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 207
    | Hs_Ensembl = ENSG00000142208
    | Hs_RefseqProtein = NP_001014431
    | Hs_RefseqmRNA = NM_001014431
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 14
    | Hs_GenLoc_start = 104306734
    | Hs_GenLoc_end = 104333125
    | Hs_Uniprot = P31749
    | Mm_EntrezGene = 11651
    | Mm_Ensembl = ENSMUSG00000001729
    | Mm_RefseqmRNA = NM_009652
    | Mm_RefseqProtein = NP_033782
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 12
    | Mm_GenLoc_start = 113101636
    | Mm_GenLoc_end = 113122084
    | Mm_Uniprot = P31750
  }}
}}
<!-- This summary is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{PBB_Summary
| section_title =
| summary_text = The serine-threonine protein kinase encoded by the AKT1 gene 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. Multiple alternatively spliced transcript variants have been found for this gene.<ref>{{cite web | title = Entrez Gene: AKT1 v-akt murine thymoma viral oncogene homolog 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=207| accessdate = }}</ref>
}}


'''RAC-alpha serine/threonine-protein kinase''' is an [[enzyme]] that in humans is encoded by the ''AKT1'' [[gene]]. This enzyme belongs to the [[Protein kinase B|AKT]] subfamily of [[serine/threonine kinases]] that contain [[SH2 domain|SH2]] (Src homology 2-like) domains.<ref>{{cite web | title = Entrez Gene: AKT1 v-akt murine thymoma viral oncogene homolog 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=207| accessdate = }}</ref> It is commonly referred to as PKB, or by both names as "Akt/PKB".
== Function ==
The [[serine-threonine protein kinase]] AKT1 is catalytically inactive in serum-starved primary and immortalized [[fibroblast]]s. 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 [[phosphorylate]]s 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 [[insulin-like growth factor 1|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 [[HER2/neu|Neu oncogene]]. A [[single-nucleotide polymorphism]] in this gene causes [[Proteus syndrome]].<ref name="pmid21793738">{{cite journal |vauthors=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 | title = A mosaic activating mutation in AKT1 associated with the Proteus syndrome | journal = N. Engl. J. Med. | volume = 365 | issue = 7 | pages = 611–9 | year = 2011 | pmid = 21793738 | pmc = 3170413 | doi = 10.1056/NEJMoa1104017 }}</ref><ref name="pmid23992099">{{cite journal | author = Cohen MM | title = Proteus syndrome review: molecular, clinical, and pathologic features | journal = Clin. Genet. | volume = 85 | issue = 2 | pages = 111–9 | year = 2014 | pmid = 23992099 | doi = 10.1111/cge.12266 }}</ref>
==History==
AKT (now also called AKT1) was originally identified as the [[oncogene]] in the transforming [[retrovirus]], AKT8.<ref name="pmid197531">{{cite journal |vauthors=Staal SP, Hartley JW, Rowe WP | title = Isolation of transforming murine leukemia viruses from mice with a high incidence of spontaneous lymphoma | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 74 | issue = 7 | pages = 3065–7 | date = July 1977 | pmid = 197531 | pmc = 431413 | doi = 10.1073/pnas.74.7.3065 | url =  }}</ref> 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.<ref name="pmid3037531">{{cite journal | author = Staal SP | title = Molecular cloning of the akt oncogene and its human homologues AKT1 and AKT2: amplification of AKT1 in a primary human gastric adenocarcinoma | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 84 | issue = 14 | pages = 5034–7 | date = July 1987 | pmid = 3037531 | pmc = 305241 | doi = 10.1073/pnas.84.14.5034 }}</ref>
In 2011, a mutation in ''AKT1'' was strongly associated with Proteus syndrome, the disease that probably affected the [[Joseph Merrick|Elephant Man]].<ref>{{cite journal |vauthors=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 | title = A Mosaic Activating Mutation in Associated with the Proteus Syndrome | journal = New England Journal of Medicine | volume = 365 | issue = 7 | pages = 110727140030013 | date = 27 July 2011 | pmid = 21793738 | pmc = 3170413 | doi = 10.1056/NEJMoa1104017 }}</ref>
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.
==Interactions==
AKT1 has been shown to [[Protein-protein interaction|interact]] with:
{{div col|colwidth=20em}}
* [[AKTIP]],<ref name = pmid14749367>{{cite journal |vauthors=Remy I, Michnick SW | title = Regulation of apoptosis by the Ft1 protein, a new modulator of protein kinase B/Akt | journal = Mol. Cell. Biol. | volume = 24 | issue = 4 | pages = 1493–504 | date = Feb 2004 | pmid = 14749367 | pmc = 344167 | doi =  10.1128/mcb.24.4.1493-1504.2004}}</ref>
* [[BRAF (gene)|BRAF]],<ref name = pmid10869359>{{cite journal |vauthors=Guan KL, Figueroa C, Brtva TR, Zhu T, Taylor J, Barber TD, Vojtek AB | title = Negative regulation of the serine/threonine kinase B-Raf by Akt | journal = J. Biol. Chem. | volume = 275 | issue = 35 | pages = 27354–9 | date = Sep 2000 | pmid = 10869359 | doi = 10.1074/jbc.M004371200 }}</ref>
* [[BRCA1]],<ref name = pmid10542266>{{cite journal |vauthors=Altiok S, Batt D, Altiok N, Papautsky A, Downward J, Roberts TM, Avraham H | title = Heregulin induces phosphorylation of BRCA1 through phosphatidylinositol 3-Kinase/AKT in breast cancer cells | journal = J. Biol. Chem. | volume = 274 | issue = 45 | pages = 32274–8 | date = Nov 1999 | pmid = 10542266 | doi =  10.1074/jbc.274.45.32274}}</ref><ref name = pmid19074868>{{cite journal |vauthors=Xiang T, Ohashi A, Huang Y, Pandita TK, Ludwig T, Powell SN, Yang Q | title = Negative Regulation of AKT Activation by BRCA1 | journal = Cancer Res. | volume = 68 | issue = 24 | pages = 10040–4 | date = Dec 2008 | pmid = 19074868 | pmc = 2605656 | doi = 10.1158/0008-5472.CAN-08-3009 }}</ref>
* [[C-Raf]],<ref name = pmid10576742>{{cite journal |vauthors=Zimmermann S, Moelling K | title = Phosphorylation and regulation of Raf by Akt (protein kinase B) | journal = Science | volume = 286 | issue = 5445 | pages = 1741–4 | date = Nov 1999 | pmid = 10576742 | doi =  10.1126/science.286.5445.1741}}</ref>
* [[CDKN1B]],<ref name = pmid12042314>{{cite journal |vauthors=Fujita N, Sato S, Katayama K, Tsuruo T | title = Akt-dependent phosphorylation of p27Kip1 promotes binding to 14-3-3 and cytoplasmic localization | journal = J. Biol. Chem. | volume = 277 | issue = 32 | pages = 28706–13 | date = Aug 2002 | pmid = 12042314 | doi = 10.1074/jbc.M203668200 }}</ref>
* [[CHUK]]<ref name = pmid10485710>{{cite journal |vauthors=Ozes ON, Mayo LD, Gustin JA, Pfeffer SR, Pfeffer LM, Donner DB | title = NF-kappaB activation by tumour necrosis factor requires the Akt serine-threonine kinase | journal = Nature | volume = 401 | issue = 6748 | pages = 82–5 | date = Sep 1999 | pmid = 10485710 | doi = 10.1038/43466 }}</ref><ref name = pmid10485711>{{cite journal |vauthors=Romashkova JA, Makarov SS | title = NF-kappaB is a target of AKT in anti-apoptotic PDGF signalling | journal = Nature | volume = 401 | issue = 6748 | pages = 86–90 | date = Sep 1999 | pmid = 10485711 | doi = 10.1038/43474 }}</ref>
* [[GAB2]],<ref name = pmid11782427>{{cite journal |vauthors=Lynch DK, Daly RJ | title = PKB-mediated negative feedback tightly regulates mitogenic signalling via Gab2 | journal = EMBO J. | volume = 21 | issue = 1-2 | pages = 72–82 | date = Jan 2002 | pmid = 11782427 | pmc = 125816 | doi =  10.1093/emboj/21.1.72}}</ref>
* [[Heat shock protein 90kDa alpha (cytosolic), member A1|HSP90AA1]],<ref name = pmid12586360>{{cite journal |vauthors=Haendeler J, Hoffmann J, Rahman S, Zeiher AM, Dimmeler S | title = Regulation of telomerase activity and anti-apoptotic function by protein-protein interaction and phosphorylation | journal = FEBS Lett. | volume = 536 | issue = 1-3 | pages = 180–6 | date = Feb 2003 | pmid = 12586360 | doi =  10.1016/s0014-5793(03)00058-9}}</ref><ref name = pmid15843522>{{cite journal |vauthors=Kawauchi K, Ihjima K, Yamada O | title = 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 | journal = J. Immunol. | volume = 174 | issue = 9 | pages = 5261–9 | date = May 2005 | pmid = 15843522 | doi =  10.4049/jimmunol.174.9.5261}}</ref><ref name = pmid10995457>{{cite journal |vauthors=Sato S, Fujita N, Tsuruo T | title = Modulation of Akt kinase activity by binding to Hsp90 | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 97 | issue = 20 | pages = 10832–7 | date = Sep 2000 | pmid = 10995457 | pmc = 27109 | doi = 10.1073/pnas.170276797 }}</ref>
* [[Integrin-linked kinase|ILK]],<ref name = pmid11825911/><ref name = pmid11313365/><ref name = pmid9736715>{{cite journal |vauthors=Delcommenne M, Tan C, Gray V, Rue L, Woodgett J, Dedhar S | title = Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 95 | issue = 19 | pages = 11211–6 | date = Sep 1998 | pmid = 9736715 | pmc = 21621 | doi =  10.1073/pnas.95.19.11211}}</ref>
* [[Keratin 10|KRT10]],<ref name = pmid11585925>{{cite journal |vauthors=Paramio JM, Segrelles C, Ruiz S, Jorcano JL | title = Inhibition of protein kinase B (PKB) and PKCzeta mediates keratin K10-induced cell cycle arrest | journal = Mol. Cell. Biol. | volume = 21 | issue = 21 | pages = 7449–59 | date = Nov 2001 | pmid = 11585925 | pmc = 99917 | doi = 10.1128/MCB.21.21.7449-7459.2001 }}</ref>
* [[MAP2K4]],<ref name = pmid11707464>{{cite journal |vauthors=Park HS, Kim MS, Huh SH, Park J, Chung J, Kang SS, Choi EJ | title = Akt (protein kinase B) negatively regulates SEK1 by means of protein phosphorylation | journal = J. Biol. Chem. | volume = 277 | issue = 4 | pages = 2573–8 | date = Jan 2002 | pmid = 11707464 | doi = 10.1074/jbc.M110299200 }}</ref>
* [[MAP3K11]],<ref name = pmid12458207>{{cite journal |vauthors=Barthwal MK, Sathyanarayana P, Kundu CN, Rana B, Pradeep A, Sharma C, Woodgett JR, Rana A | title = Negative regulation of mixed lineage kinase 3 by protein kinase B/AKT leads to cell survival | journal = J. Biol. Chem. | volume = 278 | issue = 6 | pages = 3897–902 | date = Feb 2003 | pmid = 12458207 | doi = 10.1074/jbc.M211598200 }}</ref>
* [[MAP3K8]],<ref name = pmid12138205>{{cite journal |vauthors=Kane LP, Mollenauer MN, Xu Z, Turck CW, Weiss A | title = Akt-dependent phosphorylation specifically regulates Cot induction of NF-kappa B-dependent transcription | journal = Mol. Cell. Biol. | volume = 22 | issue = 16 | pages = 5962–74 | date = Aug 2002 | pmid = 12138205 | pmc = 133991 | doi =  10.1128/mcb.22.16.5962-5974.2002}}</ref>
* [[MAPK14]],<ref name = pmid11042204>{{cite journal |vauthors=Rane MJ, Coxon PY, Powell DW, Webster R, Klein JB, Pierce W, Ping P, McLeish KR | title = p38 Kinase-dependent MAPKAPK-2 activation functions as 3-phosphoinositide-dependent kinase-2 for Akt in human neutrophils | journal = J. Biol. Chem. | volume = 276 | issue = 5 | pages = 3517–23 | date = Feb 2001 | pmid = 11042204 | doi = 10.1074/jbc.M005953200 }}</ref>
* [[MAPKAPK2]],<ref name = pmid11042204/>
* [[MARK2]],<ref name = pmid18292230>{{cite journal |vauthors=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 | title = Akt and CHIP coregulate tau degradation through coordinated interactions | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 105 | issue = 9 | pages = 3622–7 | date = Mar 2008 | pmid = 18292230 | pmc = 2265134 | doi = 10.1073/pnas.0709180105 }}</ref>
* [[MTCP1]],<ref name = pmid11707444>{{cite journal |vauthors=Laine J, Künstle G, Obata T, Noguchi M | title = Differential regulation of Akt kinase isoforms by the members of the TCL1 oncogene family | journal = J. Biol. Chem. | volume = 277 | issue = 5 | pages = 3743–51 | date = Feb 2002 | pmid = 11707444 | doi = 10.1074/jbc.M107069200 }}</ref><ref name = pmid10983986>{{cite journal |vauthors=Laine J, Künstle G, Obata T, Sha M, Noguchi M | title = The protooncogene TCL1 is an Akt kinase coactivator | journal = Mol. Cell | volume = 6 | issue = 2 | pages = 395–407 | date = Aug 2000 | pmid = 10983986 | doi =  10.1016/S1097-2765(00)00039-3}}</ref>
* [[Mammalian target of rapamycin|MTOR]],<ref name = pmid15718470>{{cite journal |vauthors=Sarbassov DD, Guertin DA, Ali SM, Sabatini DM | title = Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex | journal = Science | volume = 307 | issue = 5712 | pages = 1098–101 | date = Feb 2005 | pmid = 15718470 | doi = 10.1126/science.1106148 }}</ref><ref name = pmid10910062>{{cite journal |vauthors=Sekulić A, Hudson CC, Homme JL, Yin P, Otterness DM, Karnitz LM, Abraham RT | title = A direct linkage between the phosphoinositide 3-kinase-AKT signaling pathway and the mammalian target of rapamycin in mitogen-stimulated and transformed cells | journal = Cancer Res. | volume = 60 | issue = 13 | pages = 3504–13 | date = Jul 2000 | pmid = 10910062 | doi =  }}</ref><ref name = pmid14970221>{{cite journal |vauthors=Cheng SW, Fryer LG, Carling D, Shepherd PR | title = Thr2446 is a novel mammalian target of rapamycin (mTOR) phosphorylation site regulated by nutrient status | journal = J. Biol. Chem. | volume = 279 | issue = 16 | pages = 15719–22 | date = Apr 2004 | pmid = 14970221 | doi = 10.1074/jbc.C300534200 }}</ref>
* [[NPM1]],<ref name = pmid18931307>{{cite journal |vauthors=Lee SB, Xuan Nguyen TL, Choi JW, Lee KH, Cho SW, Liu Z, Ye K, Bae SS, Ahn JY | title = Nuclear Akt interacts with B23/NPM and protects it from proteolytic cleavage, enhancing cell survival | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 105 | issue = 43 | pages = 16584–9 | date = Oct 2008 | pmid = 18931307 | pmc = 2569968 | doi = 10.1073/pnas.0807668105  }}</ref>
* [[Nerve Growth factor IB|NR4A1]],<ref name = pmid11274386>{{cite journal |vauthors=Pekarsky Y, Hallas C, Palamarchuk A, Koval A, Bullrich F, Hirata Y, Bichi R, Letofsky J, Croce CM | title = Akt phosphorylates and regulates the orphan nuclear receptor Nur77 | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 98 | issue = 7 | pages = 3690–4 | date = Mar 2001 | pmid = 11274386 | pmc = 31113 | doi = 10.1073/pnas.051003198  }}</ref>
* [[Androgen receptor|NR3C4]],<ref name = pmid11404460>{{cite journal |vauthors=Lin HK, Yeh S, Kang HY, Chang C | title = Akt suppresses androgen-induced apoptosis by phosphorylating and inhibiting androgen receptor | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 98 | issue = 13 | pages = 7200–5 | date = Jun 2001 | pmid = 11404460 | pmc = 34646 | doi = 10.1073/pnas.121173298 }}</ref>
* [[PKN2]],<ref name = pmid10926925>{{cite journal |vauthors=Koh H, Lee KH, Kim D, Kim S, Kim JW, Chung J | title = Inhibition of Akt and its anti-apoptotic activities by tumor necrosis factor-induced protein kinase C-related kinase 2 (PRK2) cleavage | journal = J. Biol. Chem. | volume = 275 | issue = 44 | pages = 34451–8 | date = Nov 2000 | pmid = 10926925 | doi = 10.1074/jbc.M001753200 }}</ref>
* [[PRKCQ]],<ref name = pmid11410591>{{cite journal |vauthors=Bauer B, Krumböck N, Fresser F, Hochholdinger F, Spitaler M, Simm A, Uberall F, Schraven B, Baier G | title = 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 | journal = J. Biol. Chem. | volume = 276 | issue = 34 | pages = 31627–34 | date = Aug 2001 | pmid = 11410591 | doi = 10.1074/jbc.M103098200  }}</ref>
* [[Phosphoinositide-dependent kinase-1|PDPK1]],<ref name = pmid11825911>{{cite journal |vauthors=Barry FA, Gibbins JM | title = Protein kinase B is regulated in platelets by the collagen receptor glycoprotein VI | journal = J. Biol. Chem. | volume = 277 | issue = 15 | pages = 12874–8 | date = Apr 2002 | pmid = 11825911 | doi = 10.1074/jbc.M200482200 }}</ref><ref name = pmid11313365>{{cite journal |vauthors=Persad S, Attwell S, Gray V, Mawji N, Deng JT, Leung D, Yan J, Sanghera J, Walsh MP, Dedhar S | title = 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 | journal = J. Biol. Chem. | volume = 276 | issue = 29 | pages = 27462–9 | date = Jul 2001 | pmid = 11313365 | doi = 10.1074/jbc.M102940200 }}</ref>
* [[Plexin A1|PLXNA1]],<ref name = pmid15187088>{{cite journal |vauthors=Turner LJ, Nicholls S, Hall A | title = The activity of the plexin-A1 receptor is regulated by Rac | journal = J. Biol. Chem. | volume = 279 | issue = 32 | pages = 33199–205 | date = Aug 2004 | pmid = 15187088 | doi = 10.1074/jbc.M402943200 }}</ref>
* [[TCL1A]],<ref name = pmid11707444/><ref name = pmid10983986/><ref name = pmid12009899>{{cite journal |vauthors=French SW, Shen RR, Koh PJ, Malone CS, Mallick P, Teitell MA | title = A modeled hydrophobic domain on the TCL1 oncoprotein mediates association with AKT at the cytoplasmic membrane | journal = Biochemistry | volume = 41 | issue = 20 | pages = 6376–82 | date = May 2002 | pmid = 12009899 | doi =  10.1021/bi016068o}}</ref>
* [[TRIB3]],<ref name = pmid12791994>{{cite journal |vauthors=Du K, Herzig S, Kulkarni RN, Montminy M | title = TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in liver | journal = Science | volume = 300 | issue = 5625 | pages = 1574–7 | date = Jun 2003 | pmid = 12791994 | doi = 10.1126/science.1079817 }}</ref>
* [[TSC1]],<ref name = pmid12167664/><ref name = pmid15342917/>
* [[TSC2]],<ref name = pmid12167664>{{cite journal |vauthors=Dan HC, Sun M, Yang L, Feldman RI, Sui XM, Ou CC, Nellist M, Yeung RS, Halley DJ, Nicosia SV, Pledger WJ, Cheng JQ | title = Phosphatidylinositol 3-kinase/Akt pathway regulates tuberous sclerosis tumor suppressor complex by phosphorylation of tuberin | journal = J. Biol. Chem. | volume = 277 | issue = 38 | pages = 35364–70 | date = Sep 2002 | pmid = 12167664 | doi = 10.1074/jbc.M205838200 }}</ref><ref name = pmid15342917>{{cite journal |vauthors=Roux PP, Ballif BA, Anjum R, Gygi SP, Blenis J | title = Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 101 | issue = 37 | pages = 13489–94 | date = Sep 2004 | pmid = 15342917 | pmc = 518784 | doi = 10.1073/pnas.0405659101 }}</ref>  and
* [[YWHAZ]].<ref name = pmid11956222>{{cite journal |vauthors=Powell DW, Rane MJ, Chen Q, Singh S, McLeish KR | title = Identification of 14-3-3zeta as a protein kinase B/Akt substrate | journal = J. Biol. Chem. | volume = 277 | issue = 24 | pages = 21639–42 | date = Jun 2002 | pmid = 11956222 | doi = 10.1074/jbc.M203167200 }}</ref>
{{Div col end}}
{{Clear}}
==See also==
*[[AKT]] – the AKT family of proteins
*[[AKT2]] – the gene for the second member of the AKT family
*[[AKT3]] – the gene for the third member of the AKT family
*[[Proteus syndrome]]
{{PDB Gallery|geneid=207}}
{{Serine/threonine-specific protein kinases}}
{{Enzymes}}
{{Portal bar|Molecular and Cellular Biology|border=no}}


==References==
==References==
{{reflist|2}}
{{reflist}}
 
==Further reading==
==Further reading==
{{refbegin|35em}}
*{{cite journal | author = Hemmings BA | title = Akt signaling: linking membrane events to life and death decisions | journal = Science | volume = 275 | issue = 5300 | pages = 628–30 | year = 1997 | pmid = 9019819 | doi = 10.1126/science.275.5300.628 }}
*{{cite journal |vauthors=Vanhaesebroeck B, Alessi DR | title = The PI3K-PDK1 connection: more than just a road to PKB | journal = Biochem. J. | volume = 346 | issue = 3 | pages = 561–76 | year = 2000 | pmid = 10698680 | pmc = 1220886 | doi = 10.1042/0264-6021:3460561 }}
*{{cite journal |vauthors=Chan TO, Rittenhouse SE, Tsichlis PN | title = AKT/PKB and other D3 phosphoinositide-regulated kinases: kinase activation by phosphoinositide-dependent phosphorylation | journal = Annu. Rev. Biochem. | volume = 68 | issue =  | pages = 965–1014 | year = 2000 | pmid = 10872470 | doi = 10.1146/annurev.biochem.68.1.965 }}
*{{cite journal |vauthors=Pekarsky Y, Hallas C, Croce CM | title = Molecular basis of mature T-cell leukemia | journal = JAMA | volume = 286 | issue = 18 | pages = 2308–14 | year = 2001 | pmid = 11710897 | doi = 10.1001/jama.286.18.2308 }}
*{{cite journal |vauthors=Dickson LM, Rhodes CJ | title = Pancreatic beta-cell growth and survival in the onset of type 2 diabetes: a role for protein kinase B in the Akt? | journal = Am. J. Physiol. Endocrinol. Metab. | volume = 287 | issue = 2 | pages = E192–8 | year = 2004 | pmid = 15271644 | doi = 10.1152/ajpendo.00031.2004 }}
*{{cite journal | author = Manning BD | title = Balancing Akt with S6K: implications for both metabolic diseases and tumorigenesis | journal = J. Cell Biol. | volume = 167 | issue = 3 | pages = 399–403 | year = 2004 | pmid = 15533996 | pmc = 2172491 | doi = 10.1083/jcb.200408161 }}
*{{cite journal |vauthors=Shinohara M, Chung YJ, Saji M, Ringel MD | title = AKT in thyroid tumorigenesis and progression | journal = Endocrinology | volume = 148 | issue = 3 | pages = 942–7 | year = 2007 | pmid = 16946008 | doi = 10.1210/en.2006-0937 }}
{{refend}}


{{refbegin | 2}}
==External links==
{{PBB_Further_reading
*[http://www.horizondx.com/products/base-seq-qpcr.html?cat=36 AKT1 Standards] - Learn more about AKT1 Reference Controls
| citations =
* {{UCSC gene info|AKT1}}
*{{cite journal  | author=Hemmings BA |title=Akt signaling: linking membrane events to life and death decisions. |journal=Science |volume=275 |issue= 5300 |pages= 628-30 |year= 1997 |pmid= 9019819 |doi= }}
*{{cite journal  | author=Vanhaesebroeck B, Alessi DR |title=The PI3K-PDK1 connection: more than just a road to PKB. |journal=Biochem. J. |volume=346 Pt 3 |issue=  |pages= 561-76 |year= 2000 |pmid= 10698680 |doi=  }}
*{{cite journal  | author=Chan TO, Rittenhouse SE, Tsichlis PN |title=AKT/PKB and other D3 phosphoinositide-regulated kinases: kinase activation by phosphoinositide-dependent phosphorylation. |journal=Annu. Rev. Biochem. |volume=68 |issue=  |pages= 965-1014 |year= 2000 |pmid= 10872470 |doi= 10.1146/annurev.biochem.68.1.965 }}
*{{cite journal  | author=Pekarsky Y, Hallas C, Croce CM |title=Molecular basis of mature T-cell leukemia. |journal=JAMA |volume=286 |issue= 18 |pages= 2308-14 |year= 2001 |pmid= 11710897 |doi=  }}
*{{cite journal  | author=Dickson LM, Rhodes CJ |title=Pancreatic beta-cell growth and survival in the onset of type 2 diabetes: a role for protein kinase B in the Akt? |journal=Am. J. Physiol. Endocrinol. Metab. |volume=287 |issue= 2 |pages= E192-8 |year= 2004 |pmid= 15271644 |doi= 10.1152/ajpendo.00031.2004 }}
*{{cite journal  | author=Manning BD |title=Balancing Akt with S6K: implications for both metabolic diseases and tumorigenesis. |journal=J. Cell Biol. |volume=167 |issue= 3 |pages= 399-403 |year= 2004 |pmid= 15533996 |doi= 10.1083/jcb.200408161 }}
*{{cite journal  | author=Shinohara M, Chung YJ, Saji M, Ringel MD |title=AKT in thyroid tumorigenesis and progression. |journal=Endocrinology |volume=148 |issue= 3 |pages= 942-7 |year= 2007 |pmid= 16946008 |doi= 10.1210/en.2006-0937 }}
}}
{{refend}}


{{Protein-stub}}
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Latest revision as of 17:37, 5 December 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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View/Edit Human

RAC-alpha serine/threonine-protein kinase is an enzyme that in humans is encoded by the AKT1 gene. This enzyme belongs to the AKT subfamily of serine/threonine kinases that contain SH2 (Src homology 2-like) domains.[1] It is commonly referred to as PKB, or by both names as "Akt/PKB".

Function

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.[2][3]

History

AKT (now also called AKT1) was originally identified as the oncogene in the transforming retrovirus, AKT8.[4] 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.[5]

In 2011, a mutation in AKT1 was strongly associated with Proteus syndrome, the disease that probably affected the Elephant Man.[6]

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.

Interactions

AKT1 has been shown to interact with:

See also

  • AKT – the AKT family of proteins
  • AKT2 – the gene for the second member of the AKT family
  • AKT3 – the gene for the third member of the AKT family
  • Proteus syndrome

References

  1. ↑ "Entrez Gene: AKT1 v-akt murine thymoma viral oncogene homolog 1".
  2. ↑ 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 (2011). "A mosaic activating mutation in AKT1 associated with the Proteus syndrome". N. Engl. J. Med. 365 (7): 611–9. doi:10.1056/NEJMoa1104017. PMC 3170413. PMID 21793738.
  3. ↑ Cohen MM (2014). "Proteus syndrome review: molecular, clinical, and pathologic features". Clin. Genet. 85 (2): 111–9. doi:10.1111/cge.12266. PMID 23992099.
  4. ↑ Staal SP, Hartley JW, Rowe WP (July 1977). "Isolation of transforming murine leukemia viruses from mice with a high incidence of spontaneous lymphoma". Proc. Natl. Acad. Sci. U.S.A. 74 (7): 3065–7. doi:10.1073/pnas.74.7.3065. PMC 431413. PMID 197531.
  5. ↑ 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. doi:10.1073/pnas.84.14.5034. PMC 305241. PMID 3037531.
  6. ↑ 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): 110727140030013. doi:10.1056/NEJMoa1104017. PMC 3170413. PMID 21793738.
  7. ↑ Remy I, Michnick SW (Feb 2004). "Regulation of apoptosis by the Ft1 protein, a new modulator of protein kinase B/Akt". Mol. Cell. Biol. 24 (4): 1493–504. doi:10.1128/mcb.24.4.1493-1504.2004. PMC 344167. PMID 14749367.
  8. ↑ 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. PMID 10869359.
  9. ↑ 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. PMID 10542266.
  10. ↑ Xiang T, Ohashi A, Huang Y, Pandita TK, Ludwig T, Powell SN, Yang Q (Dec 2008). "Negative Regulation of AKT Activation by BRCA1". Cancer Res. 68 (24): 10040–4. doi:10.1158/0008-5472.CAN-08-3009. PMC 2605656. PMID 19074868.
  11. ↑ Zimmermann S, Moelling K (Nov 1999). "Phosphorylation and regulation of Raf by Akt (protein kinase B)". Science. 286 (5445): 1741–4. doi:10.1126/science.286.5445.1741. PMID 10576742.
  12. ↑ 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. PMID 12042314.
  13. ↑ 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". Nature. 401 (6748): 82–5. doi:10.1038/43466. PMID 10485710.
  14. ↑ Romashkova JA, Makarov SS (Sep 1999). "NF-kappaB is a target of AKT in anti-apoptotic PDGF signalling". Nature. 401 (6748): 86–90. doi:10.1038/43474. PMID 10485711.
  15. ↑ Lynch DK, Daly RJ (Jan 2002). "PKB-mediated negative feedback tightly regulates mitogenic signalling via Gab2". EMBO J. 21 (1–2): 72–82. doi:10.1093/emboj/21.1.72. PMC 125816. PMID 11782427.
  16. ↑ 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. PMID 12586360.
  17. ↑ 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. PMID 15843522.
  18. ↑ Sato S, Fujita N, Tsuruo T (Sep 2000). "Modulation of Akt kinase activity by binding to Hsp90". Proc. Natl. Acad. Sci. U.S.A. 97 (20): 10832–7. doi:10.1073/pnas.170276797. PMC 27109. PMID 10995457.
  19. ↑ 19.0 19.1 Barry 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. PMID 11825911.
  20. ↑ 20.0 20.1 Persad 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. PMID 11313365.
  21. ↑ 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. doi:10.1073/pnas.95.19.11211. PMC 21621. PMID 9736715.
  22. ↑ 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. PMC 99917. PMID 11585925.
  23. ↑ 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.
  24. ↑ 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.
  25. ↑ Kane LP, Mollenauer MN, Xu Z, Turck CW, Weiss A (Aug 2002). "Akt-dependent phosphorylation specifically regulates Cot induction of NF-kappa B-dependent transcription". Mol. Cell. Biol. 22 (16): 5962–74. doi:10.1128/mcb.22.16.5962-5974.2002. PMC 133991. PMID 12138205.
  26. ↑ 26.0 26.1 Rane 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.
  27. ↑ 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. doi:10.1073/pnas.0709180105. PMC 2265134. PMID 18292230.
  28. ↑ 28.0 28.1 Laine 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. PMID 11707444.
  29. ↑ 29.0 29.1 Laine 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.
  30. ↑ 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. doi:10.1126/science.1106148. PMID 15718470.
  31. ↑ 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.
  32. ↑ 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.
  33. ↑ 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. doi:10.1073/pnas.0807668105. PMC 2569968. PMID 18931307.
  34. ↑ 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. doi:10.1073/pnas.051003198. PMC 31113. PMID 11274386.
  35. ↑ Lin HK, Yeh S, Kang HY, Chang C (Jun 2001). "Akt suppresses androgen-induced apoptosis by phosphorylating and inhibiting androgen receptor". Proc. Natl. Acad. Sci. U.S.A. 98 (13): 7200–5. doi:10.1073/pnas.121173298. PMC 34646. PMID 11404460.
  36. ↑ 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. PMID 10926925.
  37. ↑ 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. PMID 11410591.
  38. ↑ Turner LJ, Nicholls S, Hall A (Aug 2004). "The activity of the plexin-A1 receptor is regulated by Rac". J. Biol. Chem. 279 (32): 33199–205. doi:10.1074/jbc.M402943200. PMID 15187088.
  39. ↑ 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". Biochemistry. 41 (20): 6376–82. doi:10.1021/bi016068o. PMID 12009899.
  40. ↑ Du K, Herzig S, Kulkarni RN, Montminy M (Jun 2003). "TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in liver". Science. 300 (5625): 1574–7. doi:10.1126/science.1079817. PMID 12791994.
  41. ↑ 41.0 41.1 Dan 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. PMID 12167664.
  42. ↑ 42.0 42.1 Roux PP, Ballif BA, Anjum R, Gygi SP, Blenis J (Sep 2004). "Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase". Proc. Natl. Acad. Sci. U.S.A. 101 (37): 13489–94. doi:10.1073/pnas.0405659101. PMC 518784. PMID 15342917.
  43. ↑ 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. PMID 11956222.

Further reading

External links

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