From Wikipedia, the free encyclopedia
Protein-coding gene in the species Homo sapiens
AKT2
Available structures
PDB Ortholog search:
PDBe
RCSB List of PDB id codes
1GZK ,
1GZN ,
1GZO ,
1MRV ,
1MRY ,
1O6K ,
1O6L ,
1P6S ,
2JDO ,
2JDR ,
2UW9 ,
2X39 ,
2XH5 ,
3D0E ,
3E87 ,
3E88 ,
3E8D
Identifiers
Aliases
AKT2 , v-akt murine thymoma viral oncogene homolog 2, HIHGHH, PKBB, PKBBETA, PRKBB, RAC-BETA, AKT serine/threonine kinase 2External IDs
OMIM :
164731 ;
MGI :
104874 ;
HomoloGene :
48773 ;
GeneCards :
AKT2 ;
OMA :
AKT2 - orthologs
Wikidata
AKT2 , also known as RAC-beta serine/threonine-protein kinase ,
[5] is an
enzyme that in humans is encoded by the AKT2
gene .
[6] It influences metabolite storage as part of the
insulin signal transduction pathway .
[5]
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.
[7]
AKT2 has important roles in controlling
glycogenesis ,
gluconeogenesis , and
glucose transport as part of the
insulin signal transduction pathway .
[5]
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 .
[7]
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 .
[8]
Interactions
AKT2 has been shown to
interact with:
References
^
a
b
c
GRCh38: Ensembl release 89: ENSG00000105221 –
Ensembl , May 2017
^
a
b
c
GRCm38: Ensembl release 89: ENSMUSG00000004056 –
Ensembl , May 2017
^
"Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
"Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
a
b
c Tsoukas MA, Mantzoros CS (2016-01-01), Jameson JL, De Groot LJ, de Kretser DM, Giudice LC (eds.),
"Chapter 37 - Lipodystrophy Syndromes" , Endocrinology: Adult and Pediatric (Seventh Edition) , Philadelphia: W.B. Saunders, pp. 648–661.e5,
doi :
10.1016/b978-0-323-18907-1.00037-8 ,
ISBN
978-0-323-18907-1 , retrieved 2020-12-18
^ Cheng JQ, Godwin AK, Bellacosa A, Taguchi T, Franke TF, Hamilton TC, Tsichlis PN, Testa JR (November 1992).
"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.
Bibcode :
1992PNAS...89.9267C .
doi :
10.1073/pnas.89.19.9267 .
PMC
50107 .
PMID
1409633 .
^
a
b
"Entrez Gene: AKT2 v-akt murine thymoma viral oncogene homolog 2" .
^ Heron-Milhavet L, Khouya N, Fernandez A, Lamb NJ (2011). "Akt1 and Akt2: differentiating the aktion". Histol. Histopathol . 26 (5): 651–62.
PMID
21432781 .
^ Mitsuuchi Y, Johnson SW, Sonoda G, Tanno S, Golemis EA, Testa JR (September 1999).
"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.
doi :
10.1038/sj.onc.1203080 .
PMID
10490823 .
^ Yuan ZQ, Feldman RI, Sun M, Olashaw NE, Coppola D, Sussman GE, Shelley SA, Nicosia SV, Cheng JQ (August 2002).
"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" . J. Biol. Chem . 277 (33): 29973–82.
doi :
10.1074/jbc.M203636200 .
PMID
12048203 .
^ Figueroa C, Tarras S, Taylor J, Vojtek AB (November 2003).
"Akt2 negatively regulates assembly of the POSH-MLK-JNK signaling complex" . J. Biol. Chem . 278 (48): 47922–7.
doi :
10.1074/jbc.M307357200 .
PMID
14504284 .
^ Laine J, Künstle G, Obata T, Noguchi M (February 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 .
PMID
11707444 .
^ Laine J, Künstle G, Obata T, Sha M, Noguchi M (August 2000).
"The protooncogene TCL1 is an Akt kinase coactivator" . Mol. Cell . 6 (2): 395–407.
doi :
10.1016/S1097-2765(00)00039-3 .
PMID
10983986 .
Further reading
Jones PF, Jakubowicz T, Hemmings BA (1992).
"Molecular cloning of a second form of rac protein kinase" . Cell Regul . 2 (12): 1001–9.
doi :
10.1091/mbc.2.12.1001 .
PMC
361900 .
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.
Bibcode :
1987PNAS...84.5034S .
doi :
10.1073/pnas.84.14.5034 .
PMC
305241 .
PMID
3037531 .
Cheng JQ, Ruggeri B, Klein WM, Sonoda G, Altomare DA, Watson DK, Testa JR (1996).
"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.
doi :
10.1073/pnas.93.8.3636 .
PMC
39663 .
PMID
8622988 .
Meier R, Alessi DR, Cron P, Andjelković M, Hemmings BA (1997).
"Mitogenic activation, phosphorylation, and nuclear translocation of protein kinase Bbeta" . J. Biol. Chem . 272 (48): 30491–7.
doi :
10.1074/jbc.272.48.30491 .
PMID
9374542 .
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 .
PMID
9394803 .
S2CID
6303471 .
Walker KS, Deak M, Paterson A, Hudson K, Cohen P, Alessi DR (1998).
"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.
doi :
10.1042/bj3310299 .
PMC
1219352 .
PMID
9512493 .
Joel PB, Smith J, Sturgill TW, Fisher TL, Blenis J, Lannigan DA (1998).
"pp90rsk1 regulates estrogen receptor-mediated transcription through phosphorylation of Ser-167" . Mol. Cell. Biol . 18 (4): 1978–84.
doi :
10.1128/mcb.18.4.1978 .
PMC
121427 .
PMID
9528769 .
Delcommenne M, Tan C, Gray V, Rue L, Woodgett J, Dedhar S (1998).
"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.
Bibcode :
1998PNAS...9511211D .
doi :
10.1073/pnas.95.19.11211 .
PMC
21621 .
PMID
9736715 .
Mitsuuchi Y, Johnson SW, Sonoda G, Tanno S, Golemis EA, Testa JR (1999).
"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.
doi :
10.1038/sj.onc.1203080 .
PMID
10490823 .
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 .
PMID
10491192 .
Meucci O, Fatatis A, Simen AA, Miller RJ (2000).
"Expression of CX3CR1 chemokine receptors on neurons and their role in neuronal survival" . Proc. Natl. Acad. Sci. U.S.A . 97 (14): 8075–80.
Bibcode :
2000PNAS...97.8075M .
doi :
10.1073/pnas.090017497 .
PMC
16672 .
PMID
10869418 .
Laine J, Künstle G, Obata T, Sha M, Noguchi M (2000).
"The protooncogene TCL1 is an Akt kinase coactivator" . Mol. Cell . 6 (2): 395–407.
doi :
10.1016/S1097-2765(00)00039-3 .
PMID
10983986 .
Campbell RA, Bhat-Nakshatri P, Patel NM, Constantinidou D, Ali S, Nakshatri H (2001).
"Phosphatidylinositol 3-kinase/AKT-mediated activation of estrogen receptor alpha: a new model for anti-estrogen resistance" . J. Biol. Chem . 276 (13): 9817–24.
doi :
10.1074/jbc.M010840200 .
hdl :
1805/18872 .
PMID
11139588 .
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 .
PMID
11156964 .
S2CID
26315564 .
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.
doi :
10.1152/ajprenal.2001.280.2.F333 .
PMID
11208609 .
S2CID
29992656 .
Matsumoto M, Ogawa W, Hino Y, Furukawa K, Ono Y, Takahashi M, Ohba M, Kuroki T, Kasuga M (2001).
"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.
doi :
10.1074/jbc.M011093200 .
PMID
11278835 .
Brownawell AM, Kops GJ, Macara IG, Burgering BM (2001).
"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.
doi :
10.1128/MCB.21.10.3534-3546.2001 .
PMC
100275 .
PMID
11313479 .
Clark DE, Poteet-Smith CE, Smith JA, Lannigan DA (2001).
"Rsk2 allosterically activates estrogen receptor alpha by docking to the hormone-binding domain" . EMBO J . 20 (13): 3484–94.
doi :
10.1093/emboj/20.13.3484 .
PMC
125527 .
PMID
11432835 .
Chen R, Kim O, Yang J, Sato K, Eisenmann KM, McCarthy J, Chen H, Qiu Y (2001).
"Regulation of Akt/PKB activation by tyrosine phosphorylation" . J. Biol. Chem . 276 (34): 31858–62.
doi :
10.1074/jbc.C100271200 .
PMID
11445557 .
External links
PDB gallery
1gzk : MOLECULAR MECHANISM FOR THE REGULATION OF PROTEIN KINASE B/ AKT BY HYDROPHOBIC MOTIF PHOSPHORYLATION
1gzn : STRUCTURE OF PKB KINASE DOMAIN
1gzo : STRUCTURE OF PROTEIN KINASE B UNPHOSPHORYLATED
1mrv : crystal structure of an inactive Akt2 kinase domain
1mry : crystal structure of an inactive akt2 kinase domain
1o6k : STRUCTURE OF ACTIVATED FORM OF PKB KINASE DOMAIN S474D WITH GSK3 PEPTIDE AND AMP-PNP
1o6l : CRYSTAL STRUCTURE OF AN ACTIVATED AKT/PROTEIN KINASE B (PKB-PIF CHIMERA) TERNARY COMPLEX WITH AMP-PNP AND GSK3 PEPTIDE
1p6s : Solution Structure of the Pleckstrin Homology Domain of Human Protein Kinase B beta (Pkb/Akt)
2jdo : STRUCTURE OF PKB-BETA (AKT2) COMPLEXED WITH ISOQUINOLINE-5-SULFONIC ACID (2-(2-(4-CHLOROBENZYLOXY) ETHYLAMINO)ETHYL) AMIDE
2jdr : STRUCTURE OF PKB-BETA (AKT2) COMPLEXED WITH THE INHIBITOR A-443654
2uw9 : STRUCTURE OF PKB-BETA (AKT2) COMPLEXED WITH 4-(4-CHLORO-PHENYL)-4-(4-(1H-PYRAZOL-4-YL)-PHENYL)-PIPERIDINE
Activity Regulation Classification Kinetics Types