Phosphatidylinositol -trisphosphate, abbreviated PIP3, is the product of the class I phosphoinositide 3-kinases phosphorylation of phosphatidylinositol -bisphosphate. It is a phospholipid that resides on the plasma membrane.
Discovery
In 1988, Lewis C. Cantley published a paper describing the discovery of a novel type of phosphoinositide kinase with the unprecedented ability to phosphorylate the 3' position of the inositol ring resulting in the formation of phosphatidylinositol-3-phosphate. Working independently, Alexis Traynor-Kaplan and coworkers published a paper demonstrating that a novel lipid, phosphatidylinositol 3,4,5 trisphosphate occurs naturally in human neutrophils with levels that increased rapidly following physiologic stimulation with chemotactic peptide. Subsequent studies demonstrated that in vivo the enzyme originally identified by Cantley's group prefers PtdInsP2 as a substrate, producing the product PIP3.
Function
PIP3 functions to activate downstream signaling components, the most notable one being the protein kinaseAKT, which activates downstream anabolic signaling pathways required for cell growth and survival. PtdInsP3 is dephosphorylated by the phosphatasePTEN on the 3 position, generating PIP2, and by SHIPs on the 5' position of the inositol ring, producing PIP2. The PH domain in a number of proteins binds to PtdInsP3. Such proteins include Akt/PKB, PDK1, Btk1, and ARNO. The generation of PtdInsP3 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. In many types of eukaryotic cells, the production of PtdInsP3 and recruitment of PH domain proteins to the membrane results in localized actin polymerization, leading to cellular protrusions that are important for cell migration, division, and phagocytosis. The PH domain allows binding between PtdInsP3 and G protein-coupled receptor kinases. This enhances the binding of the GRK to the plasma membrane.
