同: phosphatidylinositol 4,5-bisphosphate

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/11/19 16:03:46」(JST)

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"PIP2" redirects here. For other uses, see PIP2 (disambiguation).

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

Main article: 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-triphosphate (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

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.

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]

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. 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. (2003 Apr). "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.
^ 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.

UpToDate Contents

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English Journal

Involvement of PIP2 in RNA Polymerase I transcription.

Yildirim S, Castano E, Sobol M, Philimonenko VV, Dzijak R, Venit T, Hozák P.AbstractRNA polymerase I (Pol I) transcription is essential for the cell cycle, growth, and overall protein synthesis in eukaryotes. We found that phosphatidylinositol 4,5-bisphosphate (PIP2) is a part of the protein complex on the active ribosomal promoter during the transcription. PIP2 makes a complex with Pol I and Pol I transcription factor UBF in the nucleolus. PIP2 depletion reduces Pol I transcription which can be rescued by the addition of exogenous PIP2. In addition, PIP2 also binds directly to the pre-rRNA processing factor, fibrillarin (Fib), and co-localizes with nascent transcripts in the nucleolus. PIP2 binding to UBF and Fib modulates their binding to DNA and RNA, respectively. In conclusion, PIP2 interacts with a subset of Pol I transcription machinery, and promotes Pol I transcription.
Journal of cell science.J Cell Sci.2013 Apr 16. [Epub ahead of print]
RNA polymerase I (Pol I) transcription is essential for the cell cycle, growth, and overall protein synthesis in eukaryotes. We found that phosphatidylinositol 4,5-bisphosphate (PIP2) is a part of the protein complex on the active ribosomal promoter during the transcription. PIP2 makes a complex wit
PMID 23591814

Phosphatidylinositol 4-Phosphate 5-Kinase α Activation Critically Contributes to CD28-Dependent Signaling Responses.

Muscolini M, Camperio C, Capuano C, Caristi S, Piccolella E, Galandrini R, Tuosto L.SourceDepartment of Biology and Biotechnology Charles Darwin, Fondazione Cenci Bolognetti Pasteur Institute, Sapienza University, 00185 Rome, Italy.
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CD28 is one of the most relevant costimulatory receptors that deliver both TCR-dependent and TCR-independent signals regulating a wide range of signaling pathways crucial for cytokine and chemokine gene expressions, T cell survival, and proliferation. Most of the CD28-dependent signaling functions a
PMID 23589613

Japanese Journal

Dynamics of receptor-operated Ca(2+) currents through TRPC channels controlled via the PI(4,5)P2-PLC signaling pathway.

Frontiers in pharmacology 6, 2015-02-11
NAID 120005663278

CO₂ Transport by PIP2 Aquaporins of Barley (Special Focus Issue : Plant Response to CO₂)

Plant and cell physiology 55(2), 251-257, 2014-02
NAID 40020301716

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★リンクテーブル★

リンク元	「phosphatidylinositol 4,5-bisphosphate」「ホスファチジルイノシトール二リン酸」「PtdIns-4,5-P2」「phosphatidylinositol 3,4-bisphosphate」
関連記事	「PI」「PIP」

「phosphatidylinositol 4,5-bisphosphate」

Phosphatidylinositol 4,5-bisphosphate
	IUPAC name 1,2-Diacyl-sn-glycero-3-phospho-(1-D-myo-inositol 4,5-bisphosphate)
Identifiers
CAS number	245126-95-8
PubChem	5497157
Properties
Molecular formula	C47H80O19P3
Molar mass	1042.05 g/mol
	(verify) (what is: /?); Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
	Infobox references