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Gene Review

AKT3  -  v-akt murine thymoma viral oncogene homolog 3

Homo sapiens

Synonyms: MPPH, MPPH2, PKB gamma, PKB-GAMMA, PKBG, ...
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Disease relevance of AKT3


High impact information on AKT3


Chemical compound and disease context of AKT3


Biological context of AKT3

  • Previous studies have demonstrated that AKT1 and AKT3 are activated by heat shock and oxidative stress via both phosphatidylinositol 3-kinase-dependent and -independent pathways [10].
  • However, the reported sequence of the rat Akt3 protein differed significantly from this in that it lacked 25 amino acids in the C-terminal region, including this key regulatory serine phosphorylation site (Biochem. Biophys. Res. Commun. 216, 526-534) [11].
  • We have also mapped the rodent homologs of AKT3 to rat chromosome 13q24-->q26 and mouse chromosome 1H4-6 by FISH [12].
  • We have now cloned the human homolog of this cDNA, and we have used this clone to map the AKT3 gene to human chromosome 1q44 by fluorescence in situ hybridization (FISH) [12].
  • We report that selective activation of the Akt3 protein promotes cell survival and tumor development in 43 to 60% of nonfamilial melanomas [3].

Anatomical context of AKT3

  • It has been observed that the expression levels of AKT1, AKT2, and AKT3 vary, but the levels of phospho-Ser473 AKT and phospho-Thr308 AKT are quite unique in these cancer cell lines, and that CL-1 cells have the highest basal levels of AKT activation among these cell lines [13].
  • Furthermore, upon insulin stimulation of transfected cells, PKB gamma 1 translocates to the plasma membrane to a lesser extent than PKB gamma [14].
  • Akt1 was the predominant isoform expressed in chromaffin cells, although lower levels of Akt2 and Akt3 were also found [15].

Associations of AKT3 with chemical compounds

  • In the present studies we show that the deduced sequence of human Akt3 contains this serine and that it is phosphorylated in response to insulin [11].
  • Taken together, these results suggest that phosphorylation of the hydrophobic motif at the extreme C terminus of PKB gamma may facilitate translocation of the kinase to the membrane and/or its phosphorylation on the activation loop site by phosphoinositide-dependent protein kinase-1 [14].
  • We have reported previously the cloning and characterization of human and mouse protein kinase B gamma (PKB gamma), the third member of the PKB family of second messenger-regulated serine/threonine kinases (Brodbeck, D., Cron, P., and Hemmings, B. A. (1999) J. Biol. Chem. 274, 9133--9136) [14].
  • In vitro kinase assays using immunoprecipitation and anti-Akt1, -Akt2, and -Akt3-specific antibodies demonstrated that Akt1 is activated by estradiol in MCF-7 cells whereas Akt3 is the activated isoform in ER-negative MDA-MB231 cells, implying that selective activation of Akt subtypes plays a role in the actions of estradiol [16].
  • Cisplatin induced apoptosis in HeLa and HEC-1-A cells, but KLE cells expressing Akt2 and Akt3 remained more resistant to cisplatin [9].

Regulatory relationships of AKT3


Other interactions of AKT3

  • Neither compound inhibited Akt3 nor mutants lacking the PH (pleckstrin homology) domain at concentrations up to 250 microM [18].

Analytical, diagnostic and therapeutic context of AKT3


  1. Mutational Analysis of AKT1, AKT2 and AKT3 Genes in Common Human Carcinomas. Soung, Y.H., Lee, J.W., Nam, S.W., Lee, J.Y., Yoo, N.J., Lee, S.H. Oncology (2006) [Pubmed]
  2. The MMAC1 tumor suppressor phosphatase inhibits phospholipase C and integrin-linked kinase activity. Morimoto, A.M., Tomlinson, M.G., Nakatani, K., Bolen, J.B., Roth, R.A., Herbst, R. Oncogene (2000) [Pubmed]
  3. Deregulated Akt3 activity promotes development of malignant melanoma. Stahl, J.M., Sharma, A., Cheung, M., Zimmerman, M., Cheng, J.Q., Bosenberg, M.W., Kester, M., Sandirasegarane, L., Robertson, G.P. Cancer Res. (2004) [Pubmed]
  4. Up-regulation of Akt3 in estrogen receptor-deficient breast cancers and androgen-independent prostate cancer lines. Nakatani, K., Thompson, D.A., Barthel, A., Sakaue, H., Liu, W., Weigel, R.J., Roth, R.A. J. Biol. Chem. (1999) [Pubmed]
  5. Use of human tissue to assess the oncogenic activity of melanoma-associated mutations. Chudnovsky, Y., Adams, A.E., Robbins, P.B., Lin, Q., Khavari, P.A. Nat. Genet. (2005) [Pubmed]
  6. Activation of AKT kinases in cancer: implications for therapeutic targeting. Bellacosa, A., Kumar, C.C., Di Cristofano, A., Testa, J.R. Adv. Cancer Res. (2005) [Pubmed]
  7. A specific role for AKT3 in the genesis of ovarian cancer through modulation of G(2)-M phase transition. Cristiano, B.E., Chan, J.C., Hannan, K.M., Lundie, N.A., Marmy-Conus, N.J., Campbell, I.G., Phillips, W.A., Robbie, M., Hannan, R.D., Pearson, R.B. Cancer Res. (2006) [Pubmed]
  8. Kinetic mechanism of AKT/PKB enzyme family. Zhang, X., Zhang, S., Yamane, H., Wahl, R., Ali, A., Lofgren, J.A., Kendall, R.L. J. Biol. Chem. (2006) [Pubmed]
  9. AKT involvement in cisplatin chemoresistance of human uterine cancer cells. Gagnon, V., Mathieu, I., Sexton, E., Leblanc, K., Asselin, E. Gynecol. Oncol. (2004) [Pubmed]
  10. Inhibition of JNK by cellular stress- and tumor necrosis factor alpha-induced AKT2 through activation of the NF kappa B pathway in human epithelial Cells. Yuan, Z.Q., Feldman, R.I., Sun, M., Olashaw, N.E., Coppola, D., Sussman, G.E., Shelley, S.A., Nicosia, S.V., Cheng, J.Q. J. Biol. Chem. (2002) [Pubmed]
  11. Identification of a human Akt3 (protein kinase B gamma) which contains the regulatory serine phosphorylation site. Nakatani, K., Sakaue, H., Thompson, D.A., Weigel, R.J., Roth, R.A. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  12. Mapping of AKT3, encoding a member of the Akt/protein kinase B family, to human and rodent chromosomes by fluorescence in situ hybridization. Murthy, S.S., Tosolini, A., Taguchi, T., Testa, J.R. Cytogenet. Cell Genet. (2000) [Pubmed]
  13. Blockade of AKT activation in prostate cancer cells with a small molecule inhibitor, 9-chloro-2-methylellipticinium acetate (CMEP). Zhang, M., Fang, X., Liu, H., Wang, S., Yang, D. Biochem. Pharmacol. (2007) [Pubmed]
  14. Two splice variants of protein kinase B gamma have different regulatory capacity depending on the presence or absence of the regulatory phosphorylation site serine 472 in the carboxyl-terminal hydrophobic domain. Brodbeck, D., Hill, M.M., Hemmings, B.A. J. Biol. Chem. (2001) [Pubmed]
  15. Protein kinase B/Akt is a novel cysteine string protein kinase that regulates exocytosis release kinetics and quantal size. Evans, G.J., Barclay, J.W., Prescott, G.R., Jo, S.R., Burgoyne, R.D., Birnbaum, M.J., Morgan, A. J. Biol. Chem. (2006) [Pubmed]
  16. Estradiol rapidly activates Akt via the ErbB2 signaling pathway. Stoica, G.E., Franke, T.F., Wellstein, A., Czubayko, F., List, H.J., Reiter, R., Morgan, E., Martin, M.B., Stoica, A. Mol. Endocrinol. (2003) [Pubmed]
  17. Akt/protein kinase B isoforms are differentially regulated by epidermal growth factor stimulation. Okano, J., Gaslightwala, I., Birnbaum, M.J., Rustgi, A.K., Nakagawa, H. J. Biol. Chem. (2000) [Pubmed]
  18. Identification and characterization of pleckstrin-homology-domain-dependent and isoenzyme-specific Akt inhibitors. Barnett, S.F., Defeo-Jones, D., Fu, S., Hancock, P.J., Haskell, K.M., Jones, R.E., Kahana, J.A., Kral, A.M., Leander, K., Lee, L.L., Malinowski, J., McAvoy, E.M., Nahas, D.D., Robinson, R.G., Huber, H.E. Biochem. J. (2005) [Pubmed]
  19. Structural and functional complexity of the genomic region controlling AK-toxin biosynthesis and pathogenicity in the Japanese pear pathotype of Alternaria alternata. Tanaka, A., Tsuge, T. Mol. Plant Microbe Interact. (2000) [Pubmed]
  20. Specific inhibition of AKT2 by RNA interference results in reduction of ovarian cancer cell proliferation: Increased expression of AKT in advanced ovarian cancer. Noske, A., Kaszubiak, A., Weichert, W., Sers, C., Niesporek, S., Koch, I., Schaefer, B., Sehouli, J., Dietel, M., Lage, H., Denkert, C. Cancer Lett. (2007) [Pubmed]
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