Class IA PI3K signaling pathway

Class I PI3Ks are responsible for the production of Phosphatidylinositol 3-phosphate (PI(3)P), Phosphatidylinositol (3,4)-bisphosphate (PI(3,4)P2), and Phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P3. The PI3K is activated by G protein-coupled receptors and tyrosine kinase receptors.

Class I

The phosphoinositol-3-kinase family is divided into three different classes: Class I, Class II, and Class III. The classifications are based on primary structure, regulation, and in vitro lipid substrate specificity.

Phosphatidylinositide 3-kinases are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer. PI3Ks are a family of related intracellular signal transducer enzymes capable of phosphorylating the 3 position hydroxyl group of the inositol ring of phosphatidylinositol.

ФОСФАТИДИЛИНОЗИТОЛ-3-КИНАЗА

Class I PI3K are heterodimeric molecules composed of a regulatory and a catalytic subunit; they are further divided between IA and IB subsets on sequence similarity.

Class IA PI3K is composed of a heterodimer between a p110 catalytic subunit and a p85 regulatory subunit. There are 5 variants of the p85 regulatory subunit (p85α, p55α, p50β, p85β, and p55γ). There are also 3 variants of the p110 catalytic subunit (p110α, β, or δ). The first 3 regulatory subunits are all splice variants of the same gene (Pik3r1), the other two being expressed by other genes (Pik3r2 and Pik3r3, p85β, and p55γ). The most highly expressed regulatory subunit is p85α.

All 3 catalytic subunits are expressed by separate genes (Pik3ca, Pik3cb, and Pik3cd for p110α, p110β, and p110δ, respectively). The first two p110 isoforms are expressed in all cells, but p110δ is expressed primarily in leukocytes, and it has been suggested that it evolved in parallel with the adaptive immune system.

The regulatory p110 and catalytic p110γ subunits comprise the type IB PI3K and are encoded by a single gene each.

Phosphatidylinositol-3,4,5-trisphosphate

Дата добавления: 2014-01-14