AKT1

AKT1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1H10, 1UNP, 1UNQ, 1UNR, 2UVM, 2UZR, 2UZS, 3CQU, 3CQW, 3MV5, 3MVH, 3O96, 3OCB, 3OW4, 3QKK, 3QKL, 3QKM, 4EJN, 4EKK, 4EKL, 4GV1, 5KCV
Identifiers
Aliases	AKT1, AKT, CWS6, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA, AKT serine/threonine kinase 1
External IDs	OMIM: 164730; MGI: 87986; HomoloGene: 3785; GeneCards: AKT1; OMA:AKT1 - orthologs
Gene location (Human) Chr. Chromosome 14 (human)[1] Band 14q32.33 Start 104,769,349 bp[1] End 104,795,751 bp[1]
Gene location (Mouse) Chr. Chromosome 12 (mouse)[2] Band 12 F1|12 61.2 cM Start 112,620,255 bp[2] End 112,641,318 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in stromal cell of endometrium ganglionic eminence left adrenal cortex right adrenal gland right adrenal cortex ventricular zone right coronary artery gallbladder body of stomach muscle layer of sigmoid colon Top expressed in ventricular zone granulocyte atrium molar human fetus efferent ductule endothelial cell of lymphatic vessel submandibular gland stroma of bone marrow lip More reference expression data BioGPS More reference expression data
Gene ontology Molecular function GTPase activating protein binding kinase activity nitric-oxide synthase regulator activity ATP binding protein kinase activity protein phosphatase 2A binding enzyme binding phosphatidylinositol-3,4,5-trisphosphate binding transferase activity 14-3-3 protein binding protein binding protein serine/threonine/tyrosine kinase activity protein kinase binding protein kinase C binding nucleotide binding phosphatidylinositol-3,4-bisphosphate binding identical protein binding protein serine/threonine kinase activity protein homodimerization activity calmodulin binding Cellular component cytoplasm cytosol membrane cell-cell junction mitochondrion nucleus ciliary basal body microtubule cytoskeleton plasma membrane spindle nucleoplasm vesicle postsynapse protein-containing complex Biological process germ cell development positive regulation of glucose import cellular response to nerve growth factor stimulus positive regulation of protein phosphorylation positive regulation of lipid biosynthetic process regulation of neuron projection development activation-induced cell death of T cells response to heat regulation of cell cycle checkpoint response to organic substance response to insulin-like growth factor stimulus positive regulation of endodeoxyribonuclease activity cellular response to DNA damage stimulus regulation of protein localization platelet activation protein phosphorylation cellular response to mechanical stimulus negative regulation of long-chain fatty acid import across plasma membrane negative regulation of fatty acid beta-oxidation cell projection organization cellular response to granulocyte macrophage colony-stimulating factor stimulus positive regulation of blood vessel endothelial cell migration glucose metabolic process glycogen metabolic process regulation of glycogen biosynthetic process glycogen cell differentiation involved in embryonic placenta development cell population proliferation negative regulation of autophagy cellular response to hypoxia negative regulation of cell size endocrine pancreas development carbohydrate transport negative regulation of proteolysis insulin-like growth factor receptor signaling pathway positive regulation of protein metabolic process positive regulation of glycogen biosynthetic process glucose homeostasis labyrinthine layer blood vessel development response to oxidative stress negative regulation of gene expression positive regulation of peptidyl-serine phosphorylation cellular response to prostaglandin E stimulus positive regulation of cell growth positive regulation of nitric-oxide synthase activity maternal placenta development regulation of myelination protein ubiquitination positive regulation of vasoconstriction hyaluronan metabolic process spinal cord development cellular response to insulin stimulus cellular response to decreased oxygen levels protein autophosphorylation inflammatory response positive regulation of fat cell differentiation positive regulation of proteasomal ubiquitin-dependent protein catabolic process negative regulation of neuron death G protein-coupled receptor signaling pathway cell differentiation cellular response to peptide negative regulation of protein kinase activity phosphorylation regulation of mRNA stability negative regulation of release of cytochrome c from mitochondria execution phase of apoptosis cellular response to organic cyclic compound positive regulation of DNA-binding transcription factor activity positive regulation of glucose metabolic process nervous system development response to fluid shear stress maintenance of protein location in mitochondrion protein catabolic process negative regulation of protein kinase activity by protein phosphorylation osteoblast differentiation response to UV-A response to hormone peptidyl-threonine phosphorylation lipopolysaccharide-mediated signaling pathway positive regulation of protein localization to nucleus negative regulation of cysteine-type endopeptidase activity involved in apoptotic process intracellular signal transduction regulation of cell migration peripheral nervous system myelin maintenance nitric oxide biosynthetic process positive regulation of endothelial cell proliferation protein biosynthesis positive regulation of nitric oxide biosynthetic process cellular response to growth factor stimulus T cell costimulation regulation of nitric-oxide synthase activity ageing mammary gland epithelial cell differentiation cellular response to epidermal growth factor stimulus multicellular organism development negative regulation of JNK cascade glycogen biosynthetic process establishment of protein localization to mitochondrion apoptotic mitochondrial changes peptidyl-serine phosphorylation positive regulation of sodium ion transport response to growth hormone positive regulation of apoptotic process response to food cellular response to vascular endothelial growth factor stimulus striated muscle cell differentiation negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway negative regulation of extrinsic apoptotic signaling pathway in absence of ligand positive regulation of fibroblast migration regulation of translation positive regulation of transcription by RNA polymerase II signal transduction negative regulation of endopeptidase activity apoptotic process positive regulation of epidermal growth factor receptor signaling pathway interleukin-18-mediated signaling pathway insulin receptor signaling pathway positive regulation of smooth muscle cell proliferation regulation of signal transduction by p53 class mediator negative regulation of macroautophagy TOR signaling anoikis positive regulation of organ growth I-kappaB kinase/NF-kappaB signaling phosphatidylinositol 3-kinase signaling cellular response to reactive oxygen species NIK/NF-kappaB signaling positive regulation of transcription, DNA-templated cellular response to cadmium ion positive regulation of I-kappaB phosphorylation epidermal growth factor receptor signaling pathway positive regulation of cell population proliferation positive regulation of mitochondrial membrane potential regulation of apoptotic process negative regulation of apoptotic process positive regulation of protein localization to plasma membrane carbohydrate metabolic process activation of protein kinase B activity protein kinase B signaling negative regulation of protein kinase B signaling excitatory postsynaptic potential cellular response to tumor necrosis factor cell migration involved in sprouting angiogenesis positive regulation of gene expression cytokine-mediated signaling pathway negative regulation of protein ubiquitination negative regulation of protein binding positive regulation of cyclin-dependent protein serine/threonine kinase activity negative regulation of Notch signaling pathway negative regulation of protein serine/threonine kinase activity cellular response to oxidised low-density lipoprotein particle stimulus positive regulation of G1/S transition of mitotic cell cycle negative regulation of leukocyte cell-cell adhesion positive regulation of protein localization to cell surface negative regulation of lymphocyte migration protein import into nucleus Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 207 11651 Ensembl ENSG00000142208 ENSMUSG00000001729 UniProt P31749 P31750 RefSeq (mRNA) NM_001014431 NM_001014432 NM_005163 NM_001382430 NM_001382431 NM_001382432 NM_001382433 NM_001165894 NM_009652 NM_001331107 RefSeq (protein) NP_001014431 NP_001014432 NP_005154 NP_001369359 NP_001369360 NP_001369361 NP_001369362 NP_001159366 NP_001318036 NP_033782 Location (UCSC) Chr 14: 104.77 – 104.8 Mb Chr 12: 112.62 – 112.64 Mb PubMed search [3] [4]
Wikidata
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RAC(Rho family)-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) protein domains.^[5] 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.^[6][7]

History

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.

Interactions

AKT1 has been shown to interact with:

• AKTIP,^[11]
• BRAF,^[12]
• BRCA1,^[13][14]
• C-Raf,^[15]
• CDKN1B,^[16]
• CHUK^[17][18]
• GAB2,^[19]
• HSP90AA1,^[20][21][22]
• ILK,^[23][24][25]
• KRT10,^[26]
• MAP2K4,^[27]
• MAP3K11,^[28]
• MAP3K8,^[29]
• MAPK14,^[30]
• MAPKAPK2,^[30]
• MARK2,^[31]
• MTCP1,^[32][33]
• MTOR,^[34][35][36]
• NPM1,^[37]
• NR4A1,^[38]
• NR3C4,^[39]
• PKN2,^[40]
• PRKCQ,^[41]
• PDPK1,^[23][24]
• PLXNA1,^[42]
• TCL1A,^[32][33][43]
• TRIB3,^[44]
• TSC1,^{[45][verification needed]}
• TSC2,^{[45][verification needed]} and
• YWHAZ.^[46]

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. GRCh38: Ensembl release 89: ENSG00000142208 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000001729 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: AKT1 v-akt murine thymoma viral oncogene homolog 1".
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 (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.
7. Cohen MM (2014). "Proteus syndrome review: molecular, clinical, and pathologic features". Clin. Genet. 85 (2): 111–9. doi:10.1111/cge.12266. PMID 23992099. S2CID 204999819.
8. 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. Bibcode:1977PNAS...74.3065S. doi:10.1073/pnas.74.7.3065. PMC 431413. PMID 197531.
9. 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. PMC 305241. PMID 3037531.
10. 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. PMC 3170413. PMID 21793738.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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. Bibcode:1999Natur.401...82N. doi:10.1038/43466. PMID 10485710. S2CID 4419076.
18. Romashkova JA, Makarov SS (Sep 1999). "NF-kappaB is a target of AKT in anti-apoptotic PDGF signalling". Nature. 401 (6748): 86–90. Bibcode:1999Natur.401...86R. doi:10.1038/43474. PMID 10485711. S2CID 205033347.
19. 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.
20. 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. Bibcode:2003FEBSL.536..180H. doi:10.1016/s0014-5793(03)00058-9. PMID 12586360. S2CID 26111467.
21. 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.
22. 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. Bibcode:2000PNAS...9710832S. doi:10.1073/pnas.170276797. PMC 27109. PMID 10995457.
23. 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.
24. 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.
25. 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. PMC 21621. PMID 9736715.
26. 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.
27. 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.
28. 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.
29. 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.
30. 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.
31. 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. PMC 2265134. PMID 18292230.
32. 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.
33. 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.
34. 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.
35. 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.
36. 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.
37. 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. PMC 2569968. PMID 18931307.
38. 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. PMC 31113. PMID 11274386.
39. 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. Bibcode:2001PNAS...98.7200L. doi:10.1073/pnas.121173298. PMC 34646. PMID 11404460.
40. 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.
41. 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.
42. 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.
43. 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.
44. 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. Bibcode:2003Sci...300.1574D. doi:10.1126/science.1079817. PMID 12791994. S2CID 43360696.
45. 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. Bibcode:2004PNAS..10113489R. doi:10.1073/pnas.0405659101. PMC 518784. PMID 15342917.
46. 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

• 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. PMC 1220886. 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. PMC 2172491. 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 links

• AKT1 Standards - Learn more about AKT1 Reference Controls
• Human AKT1 genome location and AKT1 gene details page in the UCSC Genome Browser.