Phosphatidylinositol 4,5-bisphosphate

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"PIP2" redirects here. For other uses, see PIP2 (disambiguation).
Phosphatidylinositol 4,5-bisphosphate
Phosphatidylinositol-4,5-bisphosphate.svg
Names
IUPAC name
1,2-Diacyl-sn-glycero-3-phospho-(1-D-myo-inositol 4,5-bisphosphate)
Identifiers
245126-95-8 YesY
ChemSpider 21169207 N
Jmol 3D model Interactive image
PubChem 5497157
  • InChI=1S/C47H85O19P3/c1-3-5-7-9-11-13-15-17-19-20-22-24-26-28-30-32-34-36-41(49)63-39(37-61-40(48)35-33-31-29-27-25-23-21-18-16-14-12-10-8-6-4-2)38-62-69(59,60)66-45-42(50)43(51)46(64-67(53,54)55)47(44(45)52)65-68(56,57)58/h11,13,17,19,22,24,28,30,39,42-47,50-52H,3-10,12,14-16,18,20-21,23,25-27,29,31-38H2,1-2H3,(H,59,60)(H2,53,54,55)(H2,56,57,58)/p-5/b13-11-,19-17-,24-22-,30-28-/t39?,42-,43+,44+,45-,46-,47-/m1/s1 N
    Key: CNWINRVXAYPOMW-WJUYXORRSA-I N
  • InChI=1/C47H85O19P3/c1-3-5-7-9-11-13-15-17-19-20-22-24-26-28-30-32-34-36-41(49)63-39(37-61-40(48)35-33-31-29-27-25-23-21-18-16-14-12-10-8-6-4-2)38-62-69(59,60)66-45-42(50)43(51)46(64-67(53,54)55)47(44(45)52)65-68(56,57)58/h11,13,17,19,22,24,28,30,39,42-47,50-52H,3-10,12,14-16,18,20-21,23,25-27,29,31-38H2,1-2H3,(H,59,60)(H2,53,54,55)(H2,56,57,58)/p-5/b13-11-,19-17-,24-22-,30-28-/t39?,42-,43+,44+,45-,46-,47-/m1/s1
    Key: CNWINRVXAYPOMW-XHXVUCGABS
  • O=P([O-])([O-])O[C@@H]1[C@@H](O)[C@H](OP([O-])(=O)OCC(COC(=O)CCCCCCCCCCCCCCCCC)OC(=O)CCC/C=C\C/C=C\C/C=C\C/C=C\CCCCC)[C@H](O)[C@H](O)[C@H]1OP([O-])([O-])=O
Properties
C47H80O19P3
Molar mass 1042.05 g/mol
Vapor pressure {{{value}}}
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YesYN ?)
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. In metazoans, PtdIns(4,5)P2 can also be formed by type II phosphatidylinositol 5-phosphate 4-kinases from PI(5)P.[2]

The fatty acids of PtdIns(4,5)P2 are variable in different species and tissues, but studies show the most common fatty acids are stearic in position 1 and arachidonic in 2.[3]

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. PtdIns(4,5)P2 regulates the function of many membrane proteins and ion channels, such as the M-channel. The products of the PLC catalyzation of PtdIns(4,5)P2 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

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Further information: phosphatidylinositol (3,4,5)-trisphosphate

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 PtdIns(4,5)P2 for channel activity.[5][6]

Regulation

PtdIns(4,5)P2 is regulated by many different components. One emerging hypothesis is that PtdIns(4,5)P2 concentration is maintained locally. Some of the factors involved in PtdIns(4,5)P2 regulation are:[7]

  • Lipid kinases, Lipid Phosphatase
  • Lipid Transfer Proteins
  • Growth Factors, Small GTPases
  • Cell Attachment
  • Cell-Cell Interaction
  • Change in cell volume
  • Cell differentiation state
  • Cell stress

Additional images

    References

    1. ↑ Lua error in package.lua at line 80: module 'strict' not found.
    2. ↑ Rameh LE, Tolias K, Duckworth BC, Cantley LC. A new pathway for synthesis of phosphatydilinositol-4,5-bisphosphate. Nature. 1997 Nov 13;390(6656):192-6. PMID 9367159
    3. ↑ Lua error in package.lua at line 80: module 'strict' not found.
    4. ↑ GeneGlobe -> GHRH Signaling Retrieved on May 31, 2009
    5. ↑ Lua error in package.lua at line 80: module 'strict' not found.
    6. ↑ [5]
    7. ↑ Lua error in package.lua at line 80: module 'strict' not found.
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