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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/09/10 00:16:26」(JST)

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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 G_q 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.

Examples of proteins activated by PtdIns(3,4,5)P₃ are AKT, PDPK1, 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.^[3]

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]

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

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

References

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

UpToDate Contents

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English Journal

PIP kinases define PI4,5P2 signaling specificity by association with effectors.

Choi S1, Thapa N2, Tan X2, Hedman AC2, Anderson RA3.
Biochimica et biophysica acta.Biochim Biophys Acta.2015 Jun;1851(6):711-723. doi: 10.1016/j.bbalip.2015.01.009. Epub 2015 Jan 21.
Phosphatidylinositol 4,5-bisphosphate (PI4,5P2) is an essential lipid messenger with roles in all eukaryotes and most aspects of human physiology. By controlling the targeting and activity of its effectors, PI4,5P2 modulates processes, such as cell migration, vesicular trafficking, cellular morphoge
PMID 25617736

PI(4,5)P2-binding effector proteins for vesicle exocytosis.

Martin TF1.
Biochimica et biophysica acta.Biochim Biophys Acta.2015 Jun;1851(6):785-793. doi: 10.1016/j.bbalip.2014.09.017. Epub 2014 Oct 2.
PI(4,5)P2 participates directly in priming and possibly in fusion steps of Ca2+-triggered vesicle exocytosis. High concentration nanodomains of PI(4,5)P2 reside on the plasma membrane of neuroendocrine cells. A subset of vesicles that co-localize with PI(4,5)P2 domains appear to undergo preferential
PMID 25280637

Phosphoinositides in endocytosis.

Posor Y1, Eichhorn-Grünig M1, Haucke V2.
Biochimica et biophysica acta.Biochim Biophys Acta.2015 Jun;1851(6):794-804. doi: 10.1016/j.bbalip.2014.09.014. Epub 2014 Sep 28.
The internalization and subsequent endosomal trafficking of proteins and membrane along the endocytic pathway is a fundamental cellular process. Over the last two decades, this pathway has emerged to be subject to extensive regulation by phosphoinositides (PIs), phosphorylated derivatives of the min
PMID 25264171

Japanese Journal

Negatively Charged Amino Acids Near and in Transient Receptor Potential (TRP) Domain of TRPM4 Channel Are One Determinant of Its Ca2+ Sensitivity.

Yamaguchi Soichiro,Tanimoto Akira,Otsuguro Ken-ichi,Hibino Hiroshi,Ito Shigeo
The Journal of biological chemistry 289(51), 35265-35282, 2014-12-19
… Transient receptor potential (TRP) channel melastatin subfamily member 4 (TRPM4) is a broadly expressed nonselective monovalent cation channel. … TRPM4 is activated by membrane depolarization and intracellular Ca2+, which is essential for the activation. …
NAID 120005522343

Changes in PtdIns(4,5)P2 Induced by Etoposide Treatment Modulates Small Intestinal P-Glycoprotein via Radixin

Kobori Takuro,Harada Shinichi,Nakamoto Kazuo [他]
Biological & pharmaceutical bulletin 37(7), 1124–1131, 2014-07
NAID 40020103495

A Novel OCRL1 Mutation in a Patient with the Mild Phenotype of Lowe Syndrome

, , , , ,
The Tohoku Journal of Experimental Medicine 232(3), 163-166, 2014
… Lowe syndrome is caused by mutations in the gene encoding a member of the inositol polyphosphate-5-phosphatase protein family (OCRL1) on chromosome Xq26.1. … OCRL1 contains 24 exons and encodes a 105-kDa phosphatidylinositol (4,5) bisphosphate 5-phosphatase. …
NAID 130004822400

Related Pictures

★リンクテーブル★

リンク元	「ホスファチジルイノシトール2リン酸」「ホスファチジルイノシトール二リン酸」「ホスファチジルイノシトール-4,5-二リン酸」「ホフファチジルイノシトール 4,5-ビスリン酸」「PtdIns-4,5-P2」
関連記事	「bisphosphate」「phosphatidylinositol」

「ホスファチジルイノシトール2リン酸」

Phosphatidylinositol 4,5-bisphosphate
Names
	IUPAC name 1,2-Diacyl-sn-glycero-3-phospho-(1-D-myo-inositol 4,5-bisphosphate)
Identifiers
CAS Registry Number	245126-95-8
ChemSpider	21169207
	InChI 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 ; Key: CNWINRVXAYPOMW-WJUYXORRSA-I ; 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 ;
Jmol-3D images	Image
PubChem	5497157
	SMILES 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
Chemical formula	C47H80O19P3
Molar mass	1042.05 g/mol
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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	Infobox references