AKT2 explained

AKT2, also known as RAC-beta serine/threonine-protein kinase, is an enzyme that in humans is encoded by the AKT2 gene.^[1] 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.^[2]

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.^[3]

Interactions

AKT2 has been shown to interact with:

• APPL1,^[4]
• SH3RF1^[5] and
• TCL1A.^{[6] [7]}

References

Further reading

• Jones PF, Jakubowicz T, Hemmings BA . Molecular cloning of a second form of rac protein kinase. . Cell Regul. . 2 . 12 . 1001–9 . 1992 . 1801921 . 361900 . 10.1091/mbc.2.12.1001 .
• Staal SP . 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 . 1987 . 3037531 . 305241 . 10.1073/pnas.84.14.5034 . 1987PNAS...84.5034S . free .
• Cheng JQ, Ruggeri B, Klein WM, Sonoda G, Altomare DA, Watson DK, Testa JR . 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 . 8622988 . 39663 . 10.1073/pnas.93.8.3636 . free .
• Meier R, Alessi DR, Cron P, Andjelković M, Hemmings BA . Mitogenic activation, phosphorylation, and nuclear translocation of protein kinase Bbeta. . J. Biol. Chem. . 272 . 48 . 30491–7 . 1997 . 9374542 . 10.1074/jbc.272.48.30491 . free .
• Borgatti P, Zauli G, Colamussi ML, Gibellini D, Previati M, Cantley LL, Capitani S . 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 . 9394803 . 10.1002/eji.1830271110 . 6303471 .
• Walker KS, Deak M, Paterson A, Hudson K, Cohen P, Alessi DR . 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. . (Pt 1) . 299–308 . 1998 . 9512493 . 1219352 . 10.1042/bj3310299. 331 . Pt 1 .
• Joel PB, Smith J, Sturgill TW, Fisher TL, Blenis J, Lannigan DA . pp90rsk1 regulates estrogen receptor-mediated transcription through phosphorylation of Ser-167. . Mol. Cell. Biol. . 18 . 4 . 1978–84 . 1998 . 9528769 . 121427 . 10.1128/mcb.18.4.1978.
• Delcommenne M, Tan C, Gray V, Rue L, Woodgett J, Dedhar S . 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 . 9736715 . 21621 . 10.1073/pnas.95.19.11211 . 1998PNAS...9511211D . free .
• Mitsuuchi Y, Johnson SW, Sonoda G, Tanno S, Golemis EA, Testa JR . 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 . 10490823 . 10.1038/sj.onc.1203080 . free .
• Masure S, Haefner B, Wesselink JJ, Hoefnagel E, Mortier E, Verhasselt P, Tuytelaars A, Gordon R, Richardson A . Molecular cloning, expression and characterization of the human serine/threonine kinase Akt-3. . Eur. J. Biochem. . 265 . 1 . 353–60 . 1999 . 10491192 . 10.1046/j.1432-1327.1999.00774.x . free .
• Meucci O, Fatatis A, Simen AA, Miller RJ . 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 . 10869418 . 16672 . 10.1073/pnas.090017497 . 2000PNAS...97.8075M . free .
• Laine J, Künstle G, Obata T, Sha M, Noguchi M . The protooncogene TCL1 is an Akt kinase coactivator. . Mol. Cell . 6 . 2 . 395–407 . 2000 . 10983986 . 10.1016/S1097-2765(00)00039-3 . free .
• Campbell RA, Bhat-Nakshatri P, Patel NM, Constantinidou D, Ali S, Nakshatri H . 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 . 11139588 . 10.1074/jbc.M010840200 . free . 1805/18872 . free .
• Zauli G, Milani D, Mirandola P, Mazzoni M, Secchiero P, Miscia S, Capitani S . 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 . 11156964 . 10.1096/fj.00-0354com . free . 26315564 .
• Kapasi AA, Fan S, Singhal PC . 29992656 . 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 . 11208609 . 10.1152/ajprenal.2001.280.2.F333.
• Matsumoto M, Ogawa W, Hino Y, Furukawa K, Ono Y, Takahashi M, Ohba M, Kuroki T, Kasuga M . 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 . 11278835 . 10.1074/jbc.M011093200 . free .
• Brownawell AM, Kops GJ, Macara IG, Burgering BM . 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 . 11313479 . 100275 . 10.1128/MCB.21.10.3534-3546.2001 .
• Clark DE, Poteet-Smith CE, Smith JA, Lannigan DA . Rsk2 allosterically activates estrogen receptor alpha by docking to the hormone-binding domain. . EMBO J. . 20 . 13 . 3484–94 . 2001 . 11432835 . 125527 . 10.1093/emboj/20.13.3484 .
• Chen R, Kim O, Yang J, Sato K, Eisenmann KM, McCarthy J, Chen H, Qiu Y . Regulation of Akt/PKB activation by tyrosine phosphorylation. . J. Biol. Chem. . 276 . 34 . 31858–62 . 2001 . 11445557 . 10.1074/jbc.C100271200 . free .

Notes and References

1. Cheng JQ, Godwin AK, Bellacosa A, Taguchi T, Franke TF, Hamilton TC, Tsichlis PN, Testa JR . AKT2, a putative oncogene encoding a member of a subfamily of protein-serine/threonine kinases, is amplified in human ovarian carcinomas . Proc Natl Acad Sci U S A . 89 . 19 . 9267–71 . November 1992 . 1409633 . 50107 . 10.1073/pnas.89.19.9267 . 1992PNAS...89.9267C . free .
2. Web site: Entrez Gene: AKT2 v-akt murine thymoma viral oncogene homolog 2.
3. Heron-Milhavet L, Khouya N, Fernandez A, Lamb NJ . Akt1 and Akt2: differentiating the aktion . Histol. Histopathol. . 26 . 5 . 651–62 . 2011 . 21432781 .
4. Mitsuuchi Y, Johnson SW, Sonoda G, Tanno S, Golemis EA, Testa JR . 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 . September 1999 . 10490823 . 10.1038/sj.onc.1203080 . free .
5. Figueroa C, Tarras S, Taylor J, Vojtek AB . Akt2 negatively regulates assembly of the POSH-MLK-JNK signaling complex . J. Biol. Chem. . 278 . 48 . 47922–7 . November 2003 . 14504284 . 10.1074/jbc.M307357200 . free .
6. Laine J, Künstle G, Obata T, Noguchi M . Differential regulation of Akt kinase isoforms by the members of the TCL1 oncogene family . J. Biol. Chem. . 277 . 5 . 3743–51 . February 2002 . 11707444 . 10.1074/jbc.M107069200 . free .
7. Laine J, Künstle G, Obata T, Sha M, Noguchi M . The protooncogene TCL1 is an Akt kinase coactivator . Mol. Cell . 6 . 2 . 395–407 . August 2000 . 10983986 . 10.1016/S1097-2765(00)00039-3. free .