PI-3 kinase was discovered in 1985 by Lewis C. Cantley and colleagues.
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Phosphoinositid-3-kinases
HistoryThis section has been translated automatically.
DefinitionThis section has been translated automatically.
Phosphoinositide 3-kinases (PI3-kinase, PI3K) are enzymes from the group of transferases whose activity is found in all eukaryotic cells. They belong to class 2.7 according to the EC classification.
Phosphoinositide 3-kinases play an important role in signal transduction and are involved in a variety of key cellular functions, such as cell growth, proliferation, migration, differentiation, survival and cell adhesion.
General informationThis section has been translated automatically.
PI3K catalyzes the phosphorylation of the 3'-OH position on the inositol ring of certain phospholipids in the cell membrane, the so-called phosphatidylinositols. These phosphoinositides, mainly phosphatidylinositol-3,4,5-trisphosphate (PIP3), serve as docking sites for other proteins, such as protein kinase B (also called AKT) and PDK1. The major signaling pathway that PI3K activates in this way is the PI3K/Akt signaling pathway. PI3K signaling can be activated via a variety of methods. It can be B-cell receptor(BCR)-dependent or -independent (via receptor tyrosine kinases, cytokine receptors). After receptor activation, accessory molecules lead to the activation of PI3K.
An antagonist of PI3K is the phosphatase PTEN, which is an important tumor suppressor.
OccurrenceThis section has been translated automatically.
There are 3 classes of PI3K isoforms; however, only class I isoforms phosphorylate inositol lipids to form second-messenger phosphoinositides and are associated with tumorigenesis . Class I PI3K isoforms can be subdivided into class IA and class IB PI3Ks (Fruman DA 2004). Class IA includes p110a, p110b, and p110d (catalytic domains) bound by p85, p50, or p55 (regulatory domains) Fruman DA 2004). Class IB consists exclusively of p110g (catalytic domain) bound by regulatory domain p101 (Fruman DA 2004).
Classification:
- Class IA-PI3K (EC 2.7.1.153) isoforms: p110α, p110β, p110δ.
- Class IB-PI3K isoform: p110γ.
- Class II-PI3K (EC 2.7.1.154) isoforms: PI3K-C2α, PI3K-C2β, PI3K-C2γ
- Class III-PI3K (EC 2.7.1.137) isoform: Vps34
An example of a PI3K inhibitor is wortmannin.
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In humans, changes in the structure, activity or regulation of PI3K can lead to diseases such as allergies, inflammatory processes, heart disease and cancer.
LiteratureThis section has been translated automatically.
- Brazil DP et al (2001) Ten years of protein kinase B signalling: a hard Akt to follow. Trends Biochem Sci 26:657-64.
- Fruman DA (2004) Towards an understanding of isoform specificity in phosphoinositide 3-kinase signalling in lymphocytes. Biochem Soc Trans 32:315-9.
- Geering B et al. (2007) Regulation of class IA PI3Ks: is there a role for monomeric PI3K subunits? Biochem Soc Trans 35:199-203.
- Kim D et al. (2002) Akt: versatile mediator of cell survival and beyond. J Biochem Mol Biol 35:106-15.
- Koyasu S (2003) The role of PI3K in immune cells. Nat Immunol 4: 313-9.
- Luo J et al (2003) Targeting the PI3K-Akt pathway in human cancer: rationale and promise. Cancer Cell 4:257-62.
- Sarah EM et al (2012) Molecular pathways: targeting phosphoinositide 3-kinase p110-Delta in chronic lymphocytic leukemia. Clinical Cancer Research DOI: 10.1158/1078-0432.CCR-11-1402
- Vanhaesebroeck B et al (2005) Signalling by PI3K isoforms: insights from gene-targeted mice. Trends Biochem Sci 30:194-204.
- Zhang SQ et al (2002) Receptor-specific regulation of phosphatidylinositol 30 -kinase activation by the protein tyrosine phosphatase Shp2. Mol Cell Biol 22:4062-4072.