Encyclopedia of Cancer

Living Edition
| Editors: Manfred Schwab

Akt Signal Transduction Pathway

  • George Z. Cheng
  • Santo V. Nicosia
  • Jin Q. Cheng
Living reference work entry
DOI: https://doi.org/10.1007/978-3-642-27841-9_164-2

Definition

Akt, also called protein kinase B, represents a serine/threonine protein kinase subfamily. Three members of this family have been cloned to date, namely, AKT1/PKBα, AKT2/PKBβ, and AKT3/PKBγ. The overall homology between these three isoforms is >85 % at amino acid level.

Characteristics

AKT1, AKT2, and AKT3 share a very similar structure, which contains an N-terminal pleckstrin-homology (PH) domain, a central kinase domain, and a serine/threonine-rich C-terminal region (Fig. 1). The PH domain and C-terminal region between these three isoforms are more diverse (homology 73–84 % at amino acid level) as compared to the kinase domain (90–95 %), suggesting that PH and C-terminal regions may represent functional difference between AKT1, AKT2, and AKT3. All three members of Akt localize to the cytoplasm; however, they could translocate to the nucleus upon activation. In addition, they are located on different human chromosomes (AKT1 on 14q32, AKT2 on 19q13.1-13.2, and AKT3 on 1q44).

Keywords

Induce Tumor Cell Apoptosis Anticancer Drug Discovery Kinase Subfamily Ether Lipid Analogue Alkaloid Analogue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

References

  1. Bellacosa A et al (1991) A retroviral oncogene, akt, encoding a serine-threonine kinase containing an SH2-like region. Science 254:274–277CrossRefPubMedGoogle Scholar
  2. Brognard J et al (2007) PHLPP and a second isoform, PHLPP2, differentially attenuate the amplitude of Akt signaling by regulating distinct Akt isoforms. Mol Cell 25:917–931CrossRefPubMedGoogle Scholar
  3. Cheng JQ et al (1992) AKT2, a putative oncogene encoding a member of a novel subfamily of serine-threonine protein kinases, is amplified in human ovarian carcinomas. Proc Natl Acad Sci U S A 89:9267–9271CrossRefPubMedPubMedCentralGoogle Scholar
  4. Cheng JQ et al (2005) The Akt/PKB pathway: molecular target for cancer drug discovery. Oncogene 245:7482–7492CrossRefGoogle Scholar
  5. Dummler B et al (2006) Life with a single isoform of Akt: mice lacking Akt2 and Akt3 are viable but display impaired glucose homeostasis and growth deficiencies. Mol Cell Biol 26:8042–8051CrossRefPubMedPubMedCentralGoogle Scholar
  6. Guo JP et al (2011) IKBKE activates Akt independent of phosphatidylinositol 3-kinase/PDK1/mTORC2 and PH domain to sustain transformation. J Biol Chem 286:37389–37398CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • George Z. Cheng
    • 1
  • Santo V. Nicosia
    • 2
  • Jin Q. Cheng
    • 2
  1. 1.Harvard Medical SchoolBostonUSA
  2. 2.H. Lee Moffitt Cancer CenterTampaUSA