Phosphatidylinositol (3,4,5)-trisphosphate
Encyclopedia
Phosphatidylinositol-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).
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
, 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, Btk
1, 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.
Phosphatidylinositol (4,5)-bisphosphate
Phosphatidylinositol 4,5-bisphosphate or PtdInsP2, also known simply as PIP2, is a minor phospholipid component of cell membranes...
(PIP2).
Discovery
In the mid-1980s, Lewis C. CantleyLewis C. Cantley
Lewis C. Cantley is an American cell biologist and biochemist and a professor in the Departments of Systems Biology and Medicine at Harvard Medical School, and the Director of Cancer Research at the Beth Israel Deaconess Medical Center, in Boston, Massachusetts...
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 AKTAKT
Akt, also known as Protein Kinase B , is a serine/threonine protein kinase that plays a key role in multiple cellular processes such as glucose metabolism, cell proliferation, apoptosis, transcription and cell migration.-Family members:...
, which activates downstream anabolic signaling pathways required for cell growth and survival.
PtdIns(3,4,5)P3 is dephosphorylated by the phosphatase
Phosphatase
A phosphatase is an enzyme that removes a phosphate group from its substrate by hydrolysing phosphoric acid monoesters into a phosphate ion and a molecule with a free hydroxyl group . This action is directly opposite to that of phosphorylases and kinases, which attach phosphate groups to their...
PTEN
PTEN
PTEN may mean:* Patterson-UTI Energy, Inc., which trades on the NASDAQ stock market under the symbol 'PTEN'* Prime Time Entertainment Network* PTEN , a human tumour suppressor gene on chromosome 10...
on the 3 position, generating PI(4,5)P2, and by SHIPs (SH2-containing inositol phosphatase) on the 5' position of the inositol
Inositol
Inositol or cyclohexane-1,2,3,4,5,6-hexol is a chemical compound with formula 6126 or 6, a sixfold alcohol of cyclohexane. It exists in nine possible stereoisomers, of which the most prominent form, widely occurring in nature, is cis-1,2,3,5-trans-4,6-cyclohexanehexol, or myo-inositol...
ring, producing PI(3,4)P2
Phosphatidylinositol (3,4)-bisphosphate
Phosphatidylinositol -bisphosphate is a minor phospholipid component of cell membranes, yet an important second messenger...
.
The PH domain in a number of proteins binds to PtdIns(3,4,5)P3. Such proteins include Akt/PKB
AKT
Akt, also known as Protein Kinase B , is a serine/threonine protein kinase that plays a key role in multiple cellular processes such as glucose metabolism, cell proliferation, apoptosis, transcription and cell migration.-Family members:...
, PDK1, Btk
Bruton's tyrosine kinase
Bruton's tyrosine kinase is a type of kinase enzyme implicated in the primary immunodeficiency disease X-linked agammaglobulinemia . Its exact mechanism of action remains unknown, but it plays a crucial role in B cell maturation as well as mast cell activation through the high-affinity IgE receptor...
1, and ARNO
Arno
The Arno is a river in the Tuscany region of Italy. It is the most important river of central Italy after the Tiber.- Source and route :The river originates on Mount Falterona in the Casentino area of the Apennines, and initially takes a southward curve...
. The generation of PtdIns(3,4,5)P3 at the plasma membrane upon the activation of class I PI 3-kinases
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...
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.