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


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.


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).


Induce Tumor Cell Apoptosis Anticancer Drug Discovery Kinase Subfamily Ether Lipid Analogue Alkaloid Analogue 
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  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