RAC-alpha serine/threonine-protein kinase is an enzyme that in humans is encoded by the AKT1 gene. Multiple alternatively spliced transcript variants have been found for this gene.^[1]

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]

History

Akt (now also called Akt1) was originally identified as the oncogene in the transforming retrovirus, AKT8.^[3] AKT8 was isolated from an AKR mouse spontaneous thymoma cell line 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.^[4]

In 2011, a mutation in AKT1 was strongly associated with Proteus syndrome, the disease which probably affected the Elephant Man.^[5]

Interactions

AKT1 has been shown to interact with Phosphoinositide-dependent kinase-1,^[6][7] Keratin 10,^[8] Integrin-linked kinase,^[6][7][9] TSC2,^[10][11] GAB2,^[12] TRIB3,^[13] NPM1,^[14] BRCA1,^[15][16] BRAF,^[17] C-Raf,^[18] MAPK14,^[19] MARK2,^[20] MAP2K4,^[21] MTCP1,^[22][23] TCL1A,^[22][23][24] Nerve Growth factor IB,^[25] MAPKAPK2,^[19] PRKCQ,^[26] Androgen receptor,^[27] Heat shock protein 90kDa alpha (cytosolic), member A1,^[28][29][30] Plexin A1,^[31] MAP3K11,^[32] TSC1,^[10][11] MAP3K8,^[33] Mammalian target of rapamycin,^[34][35][36] PKN2,^[37] AKTIP,^[38] YWHAZ,^[39] CHUK^[40][41] and CDKN1B.^[42]

References

Further reading

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

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