Biology:AKT2

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

AKT2, also known as RAC-beta serine/threonine-protein kinase, is an enzyme that in humans is encoded by the AKT2 gene. It influences metabolite storage as part of the insulin signal transduction pathway.

Function

This gene is a putative oncogene encoding a protein belonging to the AKT subfamily of serine/threonine kinases that contain SH2-like (Src homology 2-like) domains. The encoded protein is a general protein kinase capable of phosphorylating several known proteins.

AKT2 has important roles in controlling glycogenesis, gluconeogenesis, and glucose transport as part of the insulin signal transduction pathway.

Clinical significance

The gene was shown to be amplified and overexpressed in 2 of 8 ovarian carcinoma cell lines and 2 of 15 primary ovarian tumors. Overexpression contributes to the malignant phenotype of a subset of human ductal pancreatic cancers.

Mice lacking Akt2 have a normal body mass, but display a profound diabetic phenotype, indicating that Akt2 plays a key role in signal transduction downstream of the insulin receptor. Mice lacking Akt2 show worse outcome in breast cancer initiated by the large T antigen as well as the neu oncogene.

Interactions

AKT2 has been shown to interact with:

• APPL1,
• CHUK,
• SH3RF1 and
• TCL1A.

Further reading

• "Molecular cloning of a second form of rac protein kinase.". Cell Regul. 2 (12): 1001–9. 1992. doi:10.1091/mbc.2.12.1001. PMID 1801921. 
• Staal SP (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. doi:10.1073/pnas.84.14.5034. PMID 3037531. Bibcode: 1987PNAS...84.5034S. 
• "Amplification of AKT2 in human pancreatic cells and inhibition of AKT2 expression and tumorigenicity by antisense RNA.". Proc. Natl. Acad. Sci. U.S.A. 93 (8): 3636–41. 1996. doi:10.1073/pnas.93.8.3636. PMID 8622988. 
• "Mitogenic activation, phosphorylation, and nuclear translocation of protein kinase Bbeta.". J. Biol. Chem. 272 (48): 30491–7. 1997. doi:10.1074/jbc.272.48.30491. PMID 9374542. 
• "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. 1998. doi:10.1002/eji.1830271110. PMID 9394803. 
• "Activation of protein kinase B beta and gamma isoforms by insulin in vivo and by 3-phosphoinositide-dependent protein kinase-1 in vitro: comparison with protein kinase B alpha.". Biochem. J.. 331 ( Pt 1) (Pt 1): 299–308. 1998. doi:10.1042/bj3310299. PMID 9512493. 
• "pp90rsk1 regulates estrogen receptor-mediated transcription through phosphorylation of Ser-167.". Mol. Cell. Biol. 18 (4): 1978–84. 1998. doi:10.1128/mcb.18.4.1978. PMID 9528769. 
• "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. 1998. doi:10.1073/pnas.95.19.11211. PMID 9736715. Bibcode: 1998PNAS...9511211D. 
• "Identification of a chromosome 3p14.3-21.1 gene, APPL, encoding an adaptor molecule that interacts with the oncoprotein-serine/threonine kinase AKT2.". Oncogene 18 (35): 4891–8. 1999. doi:10.1038/sj.onc.1203080. PMID 10490823. 
• "Molecular cloning, expression and characterization of the human serine/threonine kinase Akt-3.". Eur. J. Biochem. 265 (1): 353–60. 1999. doi:10.1046/j.1432-1327.1999.00774.x. PMID 10491192. 
• "Expression of CX3CR1 chemokine receptors on neurons and their role in neuronal survival.". Proc. Natl. Acad. Sci. U.S.A. 97 (14): 8075–80. 2000. doi:10.1073/pnas.090017497. PMID 10869418. Bibcode: 2000PNAS...97.8075M. 
• "The protooncogene TCL1 is an Akt kinase coactivator.". Mol. Cell 6 (2): 395–407. 2000. doi:10.1016/S1097-2765(00)00039-3. PMID 10983986. 
• "Phosphatidylinositol 3-kinase/AKT-mediated activation of estrogen receptor alpha: a new model for anti-estrogen resistance.". J. Biol. Chem. 276 (13): 9817–24. 2001. doi:10.1074/jbc.M010840200. PMID 11139588. 
• "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. 2001. doi:10.1096/fj.00-0354com. PMID 11156964. 
• "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. 2001. doi:10.1152/ajprenal.2001.280.2.F333. PMID 11208609. 
• "Inhibition of insulin-induced activation of Akt by a kinase-deficient mutant of the epsilon isozyme of protein kinase C.". J. Biol. Chem. 276 (17): 14400–6. 2001. doi:10.1074/jbc.M011093200. PMID 11278835. 
• "Inhibition of nuclear import by protein kinase B (Akt) regulates the subcellular distribution and activity of the forkhead transcription factor AFX.". Mol. Cell. Biol. 21 (10): 3534–46. 2001. doi:10.1128/MCB.21.10.3534-3546.2001. PMID 11313479. 
• "Rsk2 allosterically activates estrogen receptor alpha by docking to the hormone-binding domain.". EMBO J. 20 (13): 3484–94. 2001. doi:10.1093/emboj/20.13.3484. PMID 11432835. 
• "Regulation of Akt/PKB activation by tyrosine phosphorylation.". J. Biol. Chem. 276 (34): 31858–62. 2001. doi:10.1074/jbc.C100271200. PMID 11445557. 

External links

• Human AKT2 genome location and AKT2 gene details page in the UCSC Genome Browser.
• Overview of all the structural information available in the PDB for UniProt: P31751 (RAC-beta serine/threonine-protein kinase) at the PDBe-KB.