Phosphatidylinositol 4,5-bisphosphate

"PIP2" redirects here. For other uses, see PIP2 (disambiguation).
Phosphatidylinositol 4,5-bisphosphate
Names
IUPAC name
1,2-Diacyl-sn-glycero-3-phospho-(1-D-myo-inositol 4,5-bisphosphate)
Identifiers
245126-95-8 Yes
ChemSpider 21169207
Jmol-3D images Image
PubChem 5497157
Properties
C47H80O19P3
Molar mass 1042.05 g/mol
Except where noted otherwise, data is given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
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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 a substrate for a number of important signaling proteins.[1]

PtdIns(4,5)P2 is formed primarily by the type I phosphatidylinositol 4 phosphate 5 kinases from PI(4)P.

The fatty acids of PIP2 are variable in different species and tissues, but studies show the most common fatty acids are stearic in position 1 and arachidonic in 2.[2]

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 Gq alpha subunit. PtdIns(4,5)P2 is a substrate for hydrolysis by phospholipase C (PLC), a membrane-bound enzyme activated through protein receptors such as α1 adrenergic receptors. PIP2 regulates the function of many membrane proteins and ion channels, such as the M-channel. The products of the PLC catalyzation of PIP2 are inositol 1,4,5-trisphosphate (InsP3; IP3) and diacylglycerol (DAG), both of which function as second messengers. In this cascade, DAG remains on the cell membrane 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.

Potassium channels

Inwardly rectifying potassium channels have been shown to require docking of PIP2 for channel activity.[4][5]

Regulation

PIP2 is regulated by many different components. One emerging hypothesis is that PIP2 concentration is maintained locally. Some of the factors involved in PIP2 regulation are[6]

Additional images

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. ↑ Tanaka T, Iwawaki D, Sakamoto M, Takai Y, Morishige J, Murakami K, Satouchi K. (April 2003). "Mechanisms of accumulation of arachidonate in phosphatidylinositol in yellowtail. A comparative study of acylation systems of phospholipids in rat and the fish species Seriola quinqueradiata". Eur J Biochem 270 (7): 1466–73. doi:10.1046/j.1432-1033.2003.03512.x. PMID 12654002.
  3. ↑ GeneGlobe -> GHRH Signaling Retrieved on May 31, 2009
  4. ↑ Soom, M. "Multiple PIP2 binding sites in Kir2.1 inwardly rectifying potassium channels". FEBS letters 490 (1-2): 49. doi:10.1016/S0014-5793(01)02136-6.
  5. ↑ [5]
  6. ↑ Hilgemann, D. W. "The Complex and Intriguing Lives of PIP2 with Ion Channels and Transporters". Science's STKE 2001 (111): 19re–19. doi:10.1126/stke.2001.111.re19.