Phosphoinositid-3-kinases

PI-3 kinase was discovered in 1985 by Lewis C. Cantley and colleagues.

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.

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.

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.

In humans, changes in the structure, activity or regulation of PI3K can lead to diseases such as allergies, inflammatory processes, heart disease and cancer.

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