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AKT1

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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".

AKT1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesAKT1, AKT, CWS6, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA, AKT serine/threonine kinase 1
External IDsOMIM: 164730; MGI: 87986; HomoloGene: 3785; GeneCards: AKT1; OMA:AKT1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

207

11651

Ensembl

ENSG00000142208

ENSMUSG00000001729

UniProt

P31749

P31750

RefSeq (mRNA)

NM_001165894
NM_009652
NM_001331107

RefSeq (protein)

NP_001159366
NP_001318036
NP_033782

Location (UCSC)Chr 14: 104.77 – 104.8 MbChr 12: 112.62 – 112.64 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

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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

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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

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AKT1 has been shown to interact with:

See also

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  • 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

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000142208 – Ensembl, May 2017
  2. ^ a b c 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.
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Further reading

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