The protein encoded by this gene is a member of the AKT subfamily of serine/threonine protein kinases. AKT kinases are known to be regulators of cell signaling in response to insulin and growth factors. They are involved in a wide variety of biological processes including cell proliferation, differentiation, apoptosis, tumorigenesis, as well as glycogen synthesis and glucose uptake. This kinase has been shown to be stimulated by platelet-derived growth factor (PDGF), insulin, and insulin-like growth factor 1 (IGF1). Alternatively splice transcript variants encoding distinct isoforms have been described.[3] Mice lacking Akt3 have a normal glucose metabolism (no diabetes), have approximately normal body weight, but have a 25% reduction in brain mass. Incidentally, Akt3 is highly expressed in the brain.
↑Brodbeck D, Cron P, Hemmings BA (Apr 1999). "A human protein kinase Bgamma with regulatory phosphorylation sites in the activation loop and in the C-terminal hydrophobic domain". J Biol Chem. 274 (14): 9133–6. doi:10.1074/jbc.274.14.9133. PMID10092583.
↑Nakatani K, Sakaue H, Thompson DA, Weigel RJ, Roth RA (Jun 1999). "Identification of a human Akt3 (protein kinase B gamma) which contains the regulatory serine phosphorylation site". Biochem Biophys Res Commun. 257 (3): 906–10. doi:10.1006/bbrc.1999.0559. PMID10208883.
↑Hodgkinson CP, Sale EM, Sale GJ (2002). "Characterization of PDK2 activity against protein kinase B gamma". Biochemistry. 41 (32): 10351–9. doi:10.1021/bi026065r. PMID12162751.
Further reading
Li W, Zhang J, Bottaro DP, Pierce JH (1997). "Identification of serine 643 of protein kinase C-delta as an important autophosphorylation site for its enzymatic activity". J. Biol. Chem. 272 (39): 24550–5. doi:10.1074/jbc.272.39.24550. PMID9305920.
Borgatti P, Zauli G, Colamussi ML, Gibellini D, Previati M, Cantley LL, Capitani S (1998). "Extracellular HIV-1 Tat protein activates phosphatidylinositol 3- and Akt/PKB kinases in CD4+ T lymphoblastoid Jurkat cells". Eur. J. Immunol. 27 (11): 2805–11. doi:10.1002/eji.1830271110. PMID9394803.
Nakatani K, Thompson DA, Barthel A, Sakaue H, Liu W, Weigel RJ, Roth RA (1999). "Up-regulation of Akt3 in estrogen receptor-deficient breast cancers and androgen-independent prostate cancer lines". J. Biol. Chem. 274 (31): 21528–32. doi:10.1074/jbc.274.31.21528. PMID10419456.
Masure S, Haefner B, Wesselink JJ, Hoefnagel E, Mortier E, Verhasselt P, Tuytelaars A, Gordon R, Richardson A (1999). "Molecular cloning, expression and characterization of the human serine/threonine kinase Akt-3". Eur. J. Biochem. 265 (1): 353–60. doi:10.1046/j.1432-1327.1999.00774.x. PMID10491192.
Murthy SS, Tosolini A, Taguchi T, Testa JR (2000). "Mapping of AKT3, encoding a member of the Akt/protein kinase B family, to human and rodent chromosomes by fluorescence in situ hybridization". Cytogenet. Cell Genet. 88 (1–2): 38–40. doi:10.1159/000015481. PMID10773662.
Zauli G, Milani D, Mirandola P, Mazzoni M, Secchiero P, Miscia S, Capitani S (2001). "HIV-1 Tat protein down-regulates CREB transcription factor expression in PC12 neuronal cells through a phosphatidylinositol 3-kinase/AKT/cyclic nucleoside phosphodiesterase pathway". FASEB J. 15 (2): 483–91. doi:10.1096/fj.00-0354com. PMID11156964.
Kapasi AA, Fan S, Singhal PC (2001). "Role of 14-3-3epsilon, c-Myc/Max, and Akt phosphorylation in HIV-1 gp 120-induced mesangial cell proliferation". Am. J. Physiol. Renal Physiol. 280 (2): F333–42. PMID11208609.
Sandirasegarane L, Kester M (2001). "Enhanced stimulation of Akt-3/protein kinase B-gamma in human aortic smooth muscle cells". Biochem. Biophys. Res. Commun. 283 (1): 158–63. doi:10.1006/bbrc.2001.4739. PMID11322783.
Brodbeck D, Hill MM, Hemmings BA (2001). "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". J. Biol. Chem. 276 (31): 29550–8. doi:10.1074/jbc.M104633200. PMID11387345.
Mende I, Malstrom S, Tsichlis PN, Vogt PK, Aoki M (2001). "Oncogenic transformation induced by membrane-targeted Akt2 and Akt3". Oncogene. 20 (32): 4419–23. doi:10.1038/sj.onc.1204486. PMID11466625.
Zinda MJ, Johnson MA, Paul JD, Horn C, Konicek BW, Lu ZH, Sandusky G, Thomas JE, Neubauer BL, Lai MT, Graff JR (2001). "AKT-1, -2, and -3 are expressed in both normal and tumor tissues of the lung, breast, prostate, and colon". Clin. Cancer Res. 7 (8): 2475–9. PMID11489829.
Laine J, Künstle G, Obata T, Noguchi M (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. PMID11707444.
Deregibus MC, Cantaluppi V, Doublier S, Brizzi MF, Deambrosis I, Albini A, Camussi G (2002). "HIV-1-Tat protein activates phosphatidylinositol 3-kinase/ AKT-dependent survival pathways in Kaposi's sarcoma cells". J. Biol. Chem. 277 (28): 25195–202. doi:10.1074/jbc.M200921200. PMID11994280.
Hodgkinson CP, Sale EM, Sale GJ (2002). "Characterization of PDK2 activity against protein kinase B gamma". Biochemistry. 41 (32): 10351–9. doi:10.1021/bi026065r. PMID12162751.