Encyclopedia of Signaling Molecules

2012 Edition
| Editors: Sangdun Choi

Phosphoinositide 3-Kinase

Reference work entry
DOI: https://doi.org/10.1007/978-1-4419-0461-4_93

Synonyms

Historical Background

Phosphoinositide 3-kinase, commonly abbreviated PI3K, is one of the most well-studied enzymes in the field of signal transduction (Fruman et al. 1998; Vanhaesebroeck et al. 2010). PI3K actually refers to a family of enzymes encoded by eight genes in mammals. Orthologs of one or more PI3K genes exist in all animals as well as in yeast. These enzymes share the ability to phosphorylate the 3′-hydroxyl of the inositol head group of phosphatidylinositol (PtdIns), generating the lipid PtdIns-3-P (Fig.  1). Some members of the PI3K family can act on phosphoinositides, which are phosphorylated derivatives of PtdIns (such as PtdIns-4,5-P 2). Therefore, the family is properly referred to as phosphoinositide 3-kinases rather than simply phosphatidylinositol 3-kinases. The products of PI3Ks, generally termed 3-phosphorylated inositides (3-PIs), serve as membrane...
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References

  1. Cantley LC, Auger KR, Carpenter C, Duckworth B, Graziani A, Kapeller R, et al. Oncogenes and signal transduction. Cell. 1991;64:281–302.PubMedGoogle Scholar
  2. Deane JA, Fruman DA. Phosphoinositide 3-kinase: diverse roles in immune cell activation. Annu Rev Immunol. 2004;22:563–98.PubMedGoogle Scholar
  3. Denley A, Kang S, Karst U, Vogt PK. Oncogenic signaling of class I PI3K isoforms. Oncogene. 2008;27:2561–74.PubMedGoogle Scholar
  4. Engelman JA. Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer. 2009;9:550–62.PubMedGoogle Scholar
  5. Engelman JA, Luo J, Cantley LC. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet.. 2006;7:606–19.PubMedGoogle Scholar
  6. Foster KG, Fingar DC. Mammalian target of rapamycin (mTOR): conducting the cellular signaling symphony. J Biol Chem. 2010;285:14071–7.PubMedGoogle Scholar
  7. Fruman DA, Bismuth G. Fine tuning the immune response with PI3K. Immunol Rev. 2009;228:253–72.PubMedGoogle Scholar
  8. Fruman DA, Meyers RE, Cantley LC. Phosphoinositide kinases. Annu Rev Biochem. 1998;67:481–507.PubMedGoogle Scholar
  9. Lemmon MA. Membrane recognition by phospholipid-binding domains. Nat Rev Mol Cell Biol. 2008;9:99–111.PubMedGoogle Scholar
  10. Liu P, Cheng H, Roberts TM, Zhao JJ. Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009;8:627–44.PubMedGoogle Scholar
  11. Manning BD, Cantley LC. AKT/PKB signaling: navigating downstream. Cell. 2007;129:1261–74.PubMedGoogle Scholar
  12. Marone R, Cmiljanovic V, Giese B, Wymann MP. Targeting phosphoinositide 3-kinase: moving towards therapy. Biochim Biophys Acta. 2008;1784:159–85.PubMedGoogle Scholar
  13. Salmena L, Carracedo A, Pandolfi PP. Tenets of PTEN tumor suppression. Cell. 2008;133:403–14.PubMedGoogle Scholar
  14. Samuels Y, Ericson K. Oncogenic PI3K and its role in cancer. Curr Opin Oncol. 2006;18:77–82.PubMedGoogle Scholar
  15. Sparks CA, Guertin DA. Targeting mTOR: prospects for mTOR complex 2 inhibitors in cancer therapy. Oncogene. 2010;29(26):3733–44. Epub April 4.PubMedGoogle Scholar
  16. Vanhaesebroeck B, Guillermet-Guibert J, Graupera M, Bilanges B. The emerging mechanisms of isoform-specific PI3K signalling. Nat Rev Mol Cell Biol. 2010;11:329–41.PubMedGoogle Scholar
  17. Williams R, Berndt A, Miller S, Hon WC, Zhang X. Form and flexibility in phosphoinositide 3-kinases. Biochem Soc Trans. 2009;37:615–26.PubMedGoogle Scholar
  18. Workman P, Clarke PA, Raynaud FI, van Montfort RL. Drugging the PI3 kinome: from chemical tools to drugs in the clinic. Cancer Res. 2010;70:2146–57.PubMedGoogle Scholar
  19. Yap TA, Garrett MD, Walton MI, Raynaud F, de Bono JS, Workman P. Targeting the PI3K-AKT-mTOR pathway: progress, pitfalls, and promises. Curr Opin Pharmacol. 2008;8:393–412.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Molecular Biology & BiochemistryUniversity of CaliforniaIrvineUSA
  2. 2.Department of Molecular Biology & BiochemistryUniversity of CaliforniaIrvineUSA