Phosphatidylinositol 4,5-bisphosphate

Phosphatidylinositol 4,5-bisphosphate
Identifiers
CAS number	245126-95-8
PubChem	5497157
Properties
Molecular formula	C47H85O19P3
Molar mass	1047.09 g/mol
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)P₂, also known simply as PIP₂, is a minor phospholipid component of cell membranes. PtdIns(4,5)P₂ is enriched at the plasma membrane where it is an important substrate for a number of important signaling proteins.^[1]

PtdIns(4,5)P2₂ is formed primarily by the type I phosphatidylinositol 4 phosphate 5 kinases from PI(4)P.

Functions

IP3/DAG pathway

PtdIns(4,5)P₂ functions as an intermediate in the IP3/DAG pathway, which is initiated by ligands binding to G-protein coupled receptors activating the G_q alpha subunit. PtdIns(4,5)P₂ a substrate for hydrolysis by phospholipase C (PLC), a membrane-bound enzyme activated through protein receptors like α1 adrenergic receptors. The products of this reaction are inositol 1,4,5-triphosphate (InsP₃) and diacylglycerol (DAG), both of which function as second messengers. In this cascade, DAG remains on the cell membane and activates the signal cascade by activating protein kinase C (PKC). PKC in turn activates other cytosolic proteins by phosphorylating them. The effect of PKC could be reversed by phosphatases. IP3 enters the cytoplasm and activates IP3 receptors on the smooth endoplasmic reticulum (ER), which opens calcium channels on the smooth ER, allowing mobilization of calcium ions through specific Ca2+ channels into the cytosol. Calcium participates in the cascade by activating other proteins.

Docking phospholipids

Class I PI 3-kinases phosphorylate PtdIns(4,5)P₂ forming phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P₃). Both PtdIns(3,4,5)P₃ and PtdIns(4,5)P₂ not only act as substrates for enzymes but also serve as docking phospholipids that bind specific domains that promote the recruitment of proteins to the plasma membrane and subsequent activation of signaling cascades.

• Examples of proteins activated by PtdIns(3,4,5)P₃ are AKT, PDK1, Btk1.
• One mechanism for direct effect of PtdIns(4,5)P₂ is opening of Na+ channels as a minor function in growth hormone release by growth hormone releasing hormone.^[2]

Additional images

PIP2 cleavage to IP3 and DAG initiates intracellular calcium release and PKC activation.

References

1. ^ Strachan T, Read AP (1999). Leptospira. In: Human Molecular Genetics (2nd ed. ed.). Wiley-Liss. (via NCBI Bookshelf) ISBN 0-471-33061-2. 
2. ^ GeneGlobe -> GHRH Signaling Retrieved on May 31, 2009

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