Class I PI 3-kinases

Class I PI 3-kinases are a subgroup of the enzyme family, phosphoinositide 3-kinase that possess a common protein domain structure, substrate specificity, and method of activation. Class I PI 3-kinases are further divided into two subclasses, class IA PI 3-kinases and class IB PI 3-kinases.

Class IA PI 3-kinases

Class IA PI 3-kinases are activated by receptor tyrosine kinases (RTKs).

There are three catalytic subunits that are classified as class IA PI 3-kinases:

There are currently five regulatory subunits that are known to associate with class IA PI 3-kinases catalytic subunits:

Class IB PI 3-kinases

Class IB PI 3-kinases are activated by G-protein-coupled receptors (GPCRs).

The only known class IB PI 3-kinase catalytic subunit is p110γ.

There are two known regulatory subunits for p110γ:

See also

References

Phosphoinositide 3-kinase

Phosphatidylinositol-4,5-bisphosphate 3-kinase (also called phosphatidylinositide 3-kinases, phosphatidylinositol-3-kinases, PI 3-kinases, PI(3)Ks, PI-3Ks or by the HUGO official stem symbol for the gene family, PI3K(s)) 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 (PtdIns). The pathway, with oncogene PIK3CA and tumor suppressor PTEN, is implicated in insensitivity of cancer tumors to insulin and IGF1, and in calorie restriction.

Discovery

The discovery of PI 3-kinases by Lewis Cantley and colleagues began with their identification of a previously unknown phosphoinositide kinase associated with the polyoma middle T protein. They observed unique substrate specificity and chromatographic properties of the products of the lipid kinase, leading to the discovery that this phosphoinositide kinase had the unprecedented ability to phosphorylate phosphoinositides on the 3' position of the inositol ring. Subsequently, Cantley and colleagues demonstrated that in vivo the enzyme prefers PtdIns(4,5)P2 as a substrate, producing the novel phosphoinositide PtdIns(3,4,5)P3.