Phosphatidylinositol 4,5-bisphosphate

Last updated
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
3D model (JSmol)
ChemSpider
PubChem CID
  • 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 X mark.svgN
    Key: CNWINRVXAYPOMW-WJUYXORRSA-I X mark.svgN
  • 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
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)P2, also known simply as PIP2 or PI(4,5)P2, 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] PIP2 also forms lipid clusters [2] that sort proteins. [3] [4] [5]

Contents

PIP2 is formed primarily by the type I phosphatidylinositol 4-phosphate 5-kinases from PI(4)P. In metazoans, PIP2 can also be formed by type II phosphatidylinositol 5-phosphate 4-kinases from PI(5)P. [6]

The fatty acids of PIP2 are variable in different species and tissues, but the most common fatty acids are stearic in position 1 and arachidonic in 2. [7]

Signaling pathways

PIP2 is a part of many cellular signaling pathways, including PIP2 cycle, PI3K signalling, and PI5P metabolism. [8] Recently, it has been found in the nucleus [9] with unknown function.

Functions

Cytoskeleton dynamics near membranes

PIP2 regulates the organization, polymerization, and branching of filamentous actin (F-actin) via direct binding to F-actin regulatory proteins. [10]

Endocytosis and exocytosis

The first evidence that indicated phosphoinositides(PIs) (especially PI(4,5)P2) are important during the exocytosis process was in 1990. Emberhard et al. [11] found that the application of PI-specific phospholipase C into digitonin-permeabilized chromaffin cells decreased PI levels, and inhibited calcium-triggered exocytosis. This exocytosis inhibition was preferential for an ATP-dependent stage, indicating PI function was required for secretion. Later studies identified associated proteins necessary during this stage, such as phosphatidylinositol transfer protein , [12] and phosphoinositol-4-monophosphatase 5 kinase type Iγ (PIPKγ) , [13] which mediates PI(4,5)P2 restoration in permeable cell incubation in an ATP-dependent way. In these later studies, PI(4,5)P2 specific antibodies strongly inhibited exocytosis, thus providing direct evidence that PI(4,5)P2 plays a pivotal role during the LDCV (Large dense core vesicle) exocytosis process.[ citation needed ]

Through the use of PI-specific kinase/phosphatase identification and PI antibody/drug/blocker discovery, the role of PI (especially PI(4,5)P2) in secretion regulation was extensively investigated. Studies utilizing PHPLCδ1 domain over-expression (acting as PI(4,5)P2 buffer or blocker) , [14] PIPKIγ knockout in chromaffin cell [15] and in central nerve system, [16] PIPKIγ knockdown in beta cell lines , [17] and over-expression of membrane-tethered inositol 5-phosphatase domain of synaptojanin 1 , [18] all suggested vesicle (synaptic vesicle and LDCV) secretion were severely impaired after PI(4,5)P2 depletion or blockage. Moreover, some studies [18] [16] [15] showed an impaired/reduced RRP of those vesicles, though the docked vesicle number were not altered [15] after PI(4,5)P2 depletion, indicating a defect at a pre-fusion stage (priming stage). Follow-up studies indicated that PI(4,5)P2 interactions with CAPS, [19] Munc13 [20] and synaptotagmin1 [21] are likely to play a role in this PI(4,5)P2 dependent priming defect.

IP3/DAG pathway

PIP2 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. [22]

Docking phospholipids

Class I PI 3-kinases phosphorylate PtdIns(4,5)P2 forming phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3) and PtdIns(4,5)P2 can be converted from PtdIns4P. PtdIns4P, 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. [23] [24]

Potassium channels

Inwardly rectifying potassium channels have been shown to require docking of PIP2 for channel activity. [26] [27]

G protein-coupled receptors

PtdIns(4,5)P2 has been shown to stabilize the active states of Class A G protein-coupled receptors (GPCRs) via direct binding, and enhance their selectivity toward certain G proteins. [28]

G protein-coupled receptor kinases

PIP2 has been shown to recruit G protein-coupled receptor kinase 2 (GRK2) to the membrane by binding to the large lobe of GRK2. This stabilizes GRK2 and also orients it in a way that allows for more efficient phosphorylation of the beta adrenergic receptor, a type of GPCR. [29]

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: [30]

Related Research Articles

<span class="mw-page-title-main">Phosphatidylinositol</span> Signaling molecule

Phosphatidylinositol or inositol phospholipid is a biomolecule. It was initially called "inosite" when it was discovered by Léon Maquenne and Johann Joseph von Scherer in the late 19th century. It was discovered in bacteria but later also found in eukaryotes, and was found to be a signaling molecule.

<span class="mw-page-title-main">Inositol phosphate</span>

Inositol phosphates are a group of mono- to hexaphosphorylated inositols. Each form of inositol phosphate is distinguished by the number and position of the phosphate group on the inositol ring.

<span class="mw-page-title-main">Phosphoinositide phospholipase C</span>

Phosphoinositide phospholipase C is a family of eukaryotic intracellular enzymes that play an important role in signal transduction processes. These enzymes belong to a larger superfamily of Phospholipase C. Other families of phospholipase C enzymes have been identified in bacteria and trypanosomes. Phospholipases C are phosphodiesterases.

<span class="mw-page-title-main">Phosphatidylinositol (3,4,5)-trisphosphate</span> Chemical compound

Phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3), abbreviated PIP3, is the product of the class I phosphoinositide 3-kinases' (PI 3-kinases) phosphorylation of phosphatidylinositol (4,5)-bisphosphate (PIP2). It is a phospholipid that resides on the plasma membrane.

<span class="mw-page-title-main">Phosphoinositide 3-kinase</span> Class of enzymes

Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer.

<span class="mw-page-title-main">Phosphatidylinositol 3,4-bisphosphate</span>

Phosphatidylinositol (3,4)-bisphosphate is a minor phospholipid component of cell membranes, yet an important second messenger. The generation of PtdIns(3,4)P2 at the plasma membrane activates a number of important cell signaling pathways.

<span class="mw-page-title-main">Phosphatidylinositol 3,5-bisphosphate</span> Chemical compound

Phosphatidylinositol 3,5-bisphosphate is one of the seven phosphoinositides found in eukaryotic cell membranes. In quiescent cells, the PtdIns(3,5)P2 levels, typically quantified by HPLC, are the lowest amongst the constitutively present phosphoinositides. They are approximately 3 to 5-fold lower as compared to PtdIns3P and PtdIns5P levels, and more than 100-fold lower than the abundant PtdIns4P and PtdIns(4,5)P2. PtdIns(3,5)P2 was first reported to occur in mouse fibroblasts and budding yeast S. cerevisiae in 1997. In S. cerevisiae PtdIns(3,5)P2 levels increase dramatically during hyperosmotic shock. The response to hyperosmotic challenge is not conserved in most tested mammalian cells except for differentiated 3T3L1 adipocytes.

Phospholipase D (EC 3.1.4.4, lipophosphodiesterase II, lecithinase D, choline phosphatase, PLD; systematic name phosphatidylcholine phosphatidohydrolase) is an enzyme of the phospholipase superfamily that catalyses the following reaction

<span class="mw-page-title-main">PX domain</span>

The PX domain is a phosphoinositide-binding structural domain involved in targeting of proteins to cell membranes.

Synaptojanin is a protein involved in vesicle uncoating in neurons. This is an important regulatory lipid phosphatase. It dephosphorylates the D-5 position phosphate from phosphatidylinositol (3,4,5)-trisphosphate (PIP3) and Phosphatidylinositol (4,5)-bisphosphate(PIP2). It belongs to family of 5-phosphatases, which are structurally unrelated to D-3 inositol phosphatases like PTEN. Other members of the family of 5'phosphoinositide phosphatases include OCRL, SHIP1, SHIP2, INPP5J, INPP5E, INPP5B, INPP5A and SKIP.

<span class="mw-page-title-main">Phospholipase C</span> Class of enzymes

Phospholipase C (PLC) is a class of membrane-associated enzymes that cleave phospholipids just before the phosphate group (see figure). It is most commonly taken to be synonymous with the human forms of this enzyme, which play an important role in eukaryotic cell physiology, in particular signal transduction pathways. Phospholipase C's role in signal transduction is its cleavage of phosphatidylinositol 4,5-bisphosphate (PIP2) into diacyl glycerol (DAG) and inositol 1,4,5-trisphosphate (IP3), which serve as second messengers. Activators of each PLC vary, but typically include heterotrimeric G protein subunits, protein tyrosine kinases, small G proteins, Ca2+, and phospholipids.

<span class="mw-page-title-main">PIKFYVE</span> Protein-coding gene in the species Homo sapiens

PIKfyve, a FYVE finger-containing phosphoinositide kinase, is an enzyme that in humans is encoded by the PIKFYVE gene.

<span class="mw-page-title-main">PIP5K1A</span> Protein-coding gene in the species Homo sapiens

Phosphatidylinositol-4-phosphate 5-kinase type-1 alpha is an enzyme that in humans is encoded by the PIP5K1A gene.

<span class="mw-page-title-main">CADPS</span> Protein-coding gene in humans

Calcium-dependent secretion activator 1 is a protein that in humans is encoded by the CADPS gene.

Phosphatidylinositol 5-phosphate (PtdIns5P) is a phosphoinositide, one of the phosphorylated derivatives of phosphatidylinositol (PtdIns), that are well-established membrane-anchored regulatory molecules. Phosphoinositides participate in signaling events that control cytoskeletal dynamics, intracellular membrane trafficking, cell proliferation and many other cellular functions. Generally, phosphoinositides transduce signals by recruiting specific phosphoinositide-binding proteins to intracellular membranes.

Lewis C. Cantley is an American cell biologist and biochemist who has made significant advances to the understanding of cancer metabolism. Among his most notable contributions are the discovery and study of the enzyme PI-3-kinase, now known to be important to understanding cancer and diabetes mellitus. He is currently Meyer Director and Professor of Cancer Biology at the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine in New York City. He was formerly a professor in the Departments of Systems Biology and Medicine at Harvard Medical School, and the Director of Cancer Research at the Beth Israel Deaconess Medical Center, in Boston, Massachusetts. In 2016, he was elected Chairman of the Board for the Hope Funds for Cancer Research.

<span class="mw-page-title-main">VAC14</span> Protein-coding gene in the species Homo sapiens

Protein VAC14 homolog, also known as ArPIKfyve, is a protein that in humans is encoded by the VAC14 gene.

The insulin transduction pathway is a biochemical pathway by which insulin increases the uptake of glucose into fat and muscle cells and reduces the synthesis of glucose in the liver and hence is involved in maintaining glucose homeostasis. This pathway is also influenced by fed versus fasting states, stress levels, and a variety of other hormones.

Phosphatidylinositol-4-phosphate 5-kinases are a class of enzymes that phosphorylate phosphatidylinositol 4-phosphate. They perform this reaction on the fifth hydroxyl of the myo-inositol ring to form phosphatidylinositol 4,5-bisphosphate.

The PI(4,5)P2 cycle or simply PIP2 cycle (also known as PI cycle in past) is one of the important signalling cascades underlying many cellular functions including GPCR signaling, cytokinesis, endocytosis, and apoptosis.

References

  1. ↑ Strachan T, Read AP (1999). Leptospira. In: Human Molecular Genetics (2nd ed.). Wiley-Liss. ISBN   0-471-33061-2. (via NCBI Bookshelf).
  2. ↑ van den Bogaart, G; Meyenberg, K; Risselada, HJ; Amin, H; Willig, KI; Hubrich, BE; Dier, M; Hell, SW; Grubmüller, H; Diederichsen, U; Jahn, R (23 October 2011). "Membrane protein sequestering by ionic protein-lipid interactions". Nature. 479 (7374): 552–5. Bibcode:2011Natur.479..552V. doi:10.1038/nature10545. hdl:11858/00-001M-0000-0012-5C28-1. PMC   3409895 . PMID   22020284. S2CID   298052.
  3. ↑ Petersen, EN; Chung, HW; Nayebosadri, A; Hansen, SB (15 December 2016). "Kinetic disruption of lipid rafts is a mechanosensor for phospholipase D." Nature Communications. 7: 13873. Bibcode:2016NatCo...713873P. doi:10.1038/ncomms13873. PMC   5171650 . PMID   27976674. S2CID   14678865.
  4. ↑ Yuan, Z; Pavel, MA; Wang, H; Kwachukwu, JC; Mediouni, S; Jablonski, JA; Nettles, KW; Reddy, CB; Valente, ST; Hansen, SB (14 September 2022). "Hydroxychloroquine blocks SARS-CoV-2 entry into the endocytic pathway in mammalian cell culture". Communications Biology. 5 (1): 958. doi:10.1038/s42003-022-03841-8. PMC   9472185 . PMID   36104427. S2CID   252281018.
  5. ↑ Robinson, CV; Rohacs, T; Hansen, SB (September 2019). "Tools for Understanding Nanoscale Lipid Regulation of Ion Channels". Trends in Biochemical Sciences. 44 (9): 795–806. doi:10.1016/j.tibs.2019.04.001. PMC   6729126 . PMID   31060927. S2CID   146810646.
  6. ↑ Rameh, LE; Tolias, K; Duckworth, BC; Cantley, LC (Nov 1997). "A new pathway for synthesis of phosphatydilinositol-4,5-bisphosphate". Nature. 390 (6656): 192–6. Bibcode:1997Natur.390..192R. doi:10.1038/36621. PMID   9367159. S2CID   4403301.
  7. ↑ 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.
  8. ↑ Bulley SJ, Clarke JH, Droubi A, Giudici ML, Irvine RF (2015). "Exploring phosphatidylinositol 5-phosphate 4-kinase function". Adv Biol Regul. 57: 193–202. doi:10.1016/j.jbior.2014.09.007. PMC   4359101 . PMID   25311266.
  9. ↑ Lewis AE, Sommer L, Arntzen MØ, Strahm Y, Morrice NA, Divecha N, D'Santos CS (2011). "Identification of nuclear phosphatidylinositol 4,5-bisphosphate-interacting proteins by neomycin extraction". Mol Cell Proteomics. 10 (2): M110.003376. doi: 10.1074/mcp.M110.003376 . PMC   3033679 . PMID   21048195.
  10. ↑ Sun, Hui; Yamamoto, Masaya; Mejillano, Marisan; Yin, Helen (November 19, 1999). "Gelsolin, a Multifunctional Actin Regulatory Protein". The Journal of Biological Chemistry. 274 (47): 33179–82. doi: 10.1074/jbc.274.47.33179 . PMID   10559185.
  11. ↑ Eberhard, David A, et al. (1990). "Evidence that the inositol phospholipids are necessary for exocytosis. Loss of inositol phospholipids and inhibition of secretion in permeabilized cells caused by a bacterial phospholipase C and removal of ATP". Biochemical Journal. 268 (1): 15–25. doi:10.1042/bj2680015. PMC   1131385 . PMID   2160809.
  12. ↑ Hay, Jesse C, Thomas M (1993). "Phosphatidylinositol transfer protein required for ATP-dependent priming of Ca2+-activated secretion". Nature. 366 (6455): 572–575. doi:10.1038/366572a0. PMID   8255295. S2CID   4348488.
  13. ↑ Hay, Jesse C, et al. (1995). "ATP-dependent inositide phosphorylation required for Ca2positive-activated secretion". Nature. 374 (6518): 173–177. doi:10.1038/374173a0. PMID   7877690. S2CID   4365980.
  14. ↑ Holz RW, et al. (2000). "A pleckstrin homology domain specific for phosphatidylinositol 4, 5-bisphosphate (PtdIns-4, 5-P2) and fused to green fluorescent protein identifies plasma membrane PtdIns-4, 5-P2 as being important in exocytosis". J. Biol. Chem. 275 (23): 17878–17885. doi: 10.1074/jbc.M000925200 . PMID   10747966.
  15. 1 2 3 Gong LW, et al. (2005). "Phosphatidylinositol phosphate kinase type Iγ regulates dynamics of large dense-core vesicle fusion". PNAS. 102 (14): 5204–5209. Bibcode:2005PNAS..102.5204G. doi: 10.1073/pnas.0501412102 . PMC   555604 . PMID   15793002.
  16. 1 2 Di Paolo G, et al. (2004). "Impaired PtdIns (4, 5) P2 synthesis in nerve terminals produces defects in synaptic vesicle trafficking". Nature. 431 (7007): 415–422. doi:10.1038/nature02896. PMID   15386003. S2CID   4333681.
  17. ↑ Waselle L, et al. (2005). "Role of phosphoinositide signaling in the control of insulin exocytosis". Molecular Endocrinology. 19 (12): 3097–3106. doi: 10.1210/me.2004-0530 . PMID   16081518.
  18. 1 2 Milosevic I, et al. (2005). "Plasmalemmal phosphatidylinositol-4, 5-bisphosphate level regulates the releasable vesicle pool size in chromaffin cells". Journal of Neuroscience. 25 (10): 2557–2565. doi: 10.1523/JNEUROSCI.3761-04.2005 . PMC   6725155 . PMID   15758165.
  19. ↑ Grishanin RN, et al. (2004). "CAPS acts at a prefusion step in dense-core vesicle exocytosis as a PIP 2 binding protein". Neuron. 43 (4): 551–562. doi: 10.1016/j.neuron.2004.07.028 . PMID   15312653.
  20. ↑ Kabachinski G, et al. (2014). "CAPS and Munc13 utilize distinct PIP2-linked mechanisms to promote vesicle exocytosis". Molecular Biology of the Cell. 25 (4): 508–521. doi:10.1091/mbc.E12-11-0829. PMC   3923642 . PMID   24356451.
  21. ↑ Loewen CA, et al. (2006). "C2B polylysine motif of synaptotagmin facilitates a Ca2+-independent stage of synaptic vesicle priming in vivo". Molecular Biology of the Cell. 17 (12): 5211–5226. doi:10.1091/mbc.E06-07-0622. PMC   1679685 . PMID   16987956.
  22. ↑ Rusten, Tor Erik; Stenmark, Harald (April 2006). "Analyzing phosphoinositides and their interacting proteins". Nature Methods. 3 (4): 251–258. doi:10.1038/nmeth867. ISSN   1548-7091. PMID   16554828. S2CID   20289175.
  23. ↑ Won DH, et al. (2006). "PI (3, 4, 5) P3 and PI (4, 5) P2 lipids target proteins with polybasic clusters to the plasma membrane". Science. 314 (5804): 1458–1461. doi:10.1126/science.1134389. PMC   3579512 . PMID   17095657.
  24. ↑ Hammond G, et al. (2012). "PI4P and PI (4, 5) P2 are essential but independent lipid determinants of membrane identity". Science. 337 (6095): 727–730. doi:10.1126/science.1222483. PMC   3646512 . PMID   22722250.
  25. ↑ GeneGlobe -> GHRH Signaling [ permanent dead link ] Retrieved on May 31, 2009
  26. ↑ Soom, M (2001). "Multiple PtdIns(4,5)P2 binding sites in Kir2.1 inwardly rectifying potassium channels". FEBS Letters. 490 (1–2): 49–53. doi: 10.1016/S0014-5793(01)02136-6 . PMID   11172809. S2CID   36375203.
  27. ↑ Hansen, SB; Tao, X; MacKinnon, R (28 August 2011). "Structural basis of PIP2 activation of the classical inward rectifier K+ channel Kir2.2". Nature. 477 (7365): 495–8. doi:10.1038/nature10370. PMC   3324908 . PMID   21874019.
  28. ↑ Yen, Hsin-Yung; Hoi, Kin Kuan; Liko, Idlir; Hedger, George; Horrell, Michael R.; Song, Wanling; Wu, Di; Heine, Philipp; Warne, Tony (2018-07-11). "PtdIns(4,5)P2 stabilizes active states of GPCRs and enhances selectivity of G-protein coupling". Nature. 559 (7714): 423–427. doi:10.1038/s41586-018-0325-6. ISSN   0028-0836. PMC   6059376 . PMID   29995853.
  29. ↑ Yang, Pei; Homan, Kristoff T.; Li, Yaoxin; Cruz-Rodríguez, Osvaldo; Tesmer, John J.G.; Chen, Zhan (2016-05-24). "Effect of Lipid Composition on Membrane Orientation of the G protein-coupled Receptor Kinase 2-Gβ1γ2 Complex". Biochemistry. 55 (20): 2841–2848. doi:10.1021/acs.biochem.6b00354. ISSN   0006-2960. PMC   4886744 . PMID   27088923.
  30. ↑ Hilgemann, D. W. (2001). "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. PMID   11734659. S2CID   24745275.

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