Phosphatidylinositol (3,4,5)-trisphosphate

Phosphatidylinositol (3,4,5)-triphosphate (PtdIns(3,4,5)P3), abbreviated PIP3, is the product of the class I phosphoinositide 3-kinases (PI 3-kinases) phosphorylation on phosphatidylinositol (4,5)-bisphosphate (PIP2).

Discovery
In the mid-1980s, Lewis C. Cantley published a series of papers describing the discovery of a novel type of phosphoinositide kinase with the unprecedented ability to phosphorylate the 3' position of the inositol ring. Subsequent studies demonstrated that in vivo the enzyme prefers PtdIns(4,5)P2 as a substrate, producing the product PIP3. PIP3 had been previously identified in human neutrophils following stimulation with chemotactic peptide

Function
PIP3 functions to activate downstream signaling components, the most notable one being the protein kinase AKT, which activates downstream anabolic signaling pathways required for cell growth and survival.

PtdIns(3,4,5)P3 is dephosphorylated by the phosphatase PTEN on the 3 position, generating PI(4,5)P2, and by SHIPs (SH2-containing inositol phosphatase) on the 5' position of the inositol ring, producing PI(3,4)P2.

The PH domain in a number of proteins binds to PtdIns(3,4,5)P3. Such proteins include Akt/PKB, PDK1, Btk1, and ARNO. The generation of PtdIns(3,4,5)P3 at the plasma membrane upon the activation of class I PI 3-kinases causes these proteins to translocate to the plasma membrane and affects their activity accordingly.

The PH domain allows binding between PtdIns(3,4,5)P3 and G protein-coupled receptor kinases (GRKs). This enhances the binding of the GRK to the plasma membrane.