PLD2

Phosphatidylcholine (PC)-specific phospholipases D (PLDs) catalyze the hydrolysis of PC to produce phosphatidic acid and choline. Activation of PC-specific PLDs occurs as a consequence of agonist stimulation of both tyrosine kinase and G protein-coupled receptors. PC-specific PLDs have been proposed to function in regulated secretion, cytoskeletal reorganization, transcriptional regulation, and cell cycle control.[supplied by OMIM]{{cite web | title = Entrez Gene: PLD2 phospholipase D2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5338}}

PLD2 is activated by substrate presentation.{{cite journal | vauthors = Petersen EN, Chung HW, Nayebosadri A, Hansen SB | title = Kinetic disruption of lipid rafts is a mechanosensor for phospholipase D | journal = Nature Communications | volume = 7 | pages = 13873 | date = December 2016 | pmid = 27976674 | pmc = 5171650 | doi = 10.1038/ncomms13873 | bibcode = 2016NatCo...713873P }} The enzyme is palmitoylated, which drives PLD2 to lipid rafts. PC substrate is polyunsaturated and resides in the membrane separately from lipid rafts near phosphatidylinositol 4,5-bisphosphate (PIP2). When PIP2 levels increase, PLD2 trafficks to PIP2 where it encounters its substrate PC. Scaffolding proteins that interact with PLD2 likely changes its preference of lipid rafts vs PIP2.

PLD2 has been shown to interact with:

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• ARF1,{{cite journal | vauthors = Lee S, Park JB, Kim JH, Kim Y, Kim JH, Shin KJ, Lee JS, Ha SH, Suh PG, Ryu SH | display-authors = 6 | title = Actin directly interacts with phospholipase D, inhibiting its activity | journal = The Journal of Biological Chemistry | volume = 276 | issue = 30 | pages = 28252–60 | date = July 2001 | pmid = 11373276 | doi = 10.1074/jbc.M008521200 | doi-access = free }}{{cite journal | vauthors = Park JB, Kim JH, Kim Y, Ha SH, Yoo JS, Du G, Frohman MA, Suh PG, Ryu SH | display-authors = 6 | title = Cardiac phospholipase D2 localizes to sarcolemmal membranes and is inhibited by alpha-actinin in an ADP-ribosylation factor-reversible manner | journal = The Journal of Biological Chemistry | volume = 275 | issue = 28 | pages = 21295–301 | date = July 2000 | pmid = 10801846 | doi = 10.1074/jbc.M002463200 | doi-access = free }}
• Aldolase A,{{cite journal | vauthors = Kim JH, Lee S, Kim JH, Lee TG, Hirata M, Suh PG, Ryu SH | title = Phospholipase D2 directly interacts with aldolase via Its PH domain | journal = Biochemistry | volume = 41 | issue = 10 | pages = 3414–21 | date = March 2002 | pmid = 11876650 | doi = 10.1021/bi015700a }}
• Amphiphysin,
• BIN1,{{cite journal | vauthors = Lee C, Kim SR, Chung JK, Frohman MA, Kilimann MW, Rhee SG | title = Inhibition of phospholipase D by amphiphysins | journal = The Journal of Biological Chemistry | volume = 275 | issue = 25 | pages = 18751–8 | date = June 2000 | pmid = 10764771 | doi = 10.1074/jbc.M001695200 | doi-access = free }}
• Caveolin 1,{{cite journal | vauthors = Zheng X, Bollinger Bollag W | title = Aquaporin 3 colocates with phospholipase d2 in caveolin-rich membrane microdomains and is downregulated upon keratinocyte differentiation | journal = The Journal of Investigative Dermatology | volume = 121 | issue = 6 | pages = 1487–95 | date = December 2003 | pmid = 14675200 | doi = 10.1111/j.1523-1747.2003.12614.x | doi-access = free }}{{cite journal | vauthors = Czarny M, Fiucci G, Lavie Y, Banno Y, Nozawa Y, Liscovitch M | title = Phospholipase D2: functional interaction with caveolin in low-density membrane microdomains | journal = FEBS Letters | volume = 467 | issue = 2–3 | pages = 326–32 | date = February 2000 | pmid = 10675563 | doi = 10.1016/s0014-5793(00)01174-1 | s2cid = 21891748 | doi-access = free }}
• Glyceraldehyde 3-phosphate dehydrogenase,{{cite journal | vauthors = Kim JH, Lee S, Park JB, Lee SD, Kim JH, Ha SH, Hasumi K, Endo A, Suh PG, Ryu SH | display-authors = 6 | title = Hydrogen peroxide induces association between glyceraldehyde 3-phosphate dehydrogenase and phospholipase D2 to facilitate phospholipase D2 activation in PC12 cells | journal = Journal of Neurochemistry | volume = 85 | issue = 5 | pages = 1228–36 | date = June 2003 | pmid = 12753082 | doi = 10.1046/j.1471-4159.2003.01755.x | s2cid = 27513985 }}
• PLCG1,{{cite journal | vauthors = Jang IH, Lee S, Park JB, Kim JH, Lee CS, Hur EM, Kim IS, Kim KT, Yagisawa H, Suh PG, Ryu SH | display-authors = 6 | title = The direct interaction of phospholipase C-gamma 1 with phospholipase D2 is important for epidermal growth factor signaling | journal = The Journal of Biological Chemistry | volume = 278 | issue = 20 | pages = 18184–90 | date = May 2003 | pmid = 12646582 | doi = 10.1074/jbc.M208438200 | doi-access = free }}
• PRKCD,{{cite journal | vauthors = Han JM, Kim JH, Lee BD, Lee SD, Kim Y, Jung YW, Lee S, Cho W, Ohba M, Kuroki T, Suh PG, Ryu SH | display-authors = 6 | title = Phosphorylation-dependent regulation of phospholipase D2 by protein kinase C delta in rat Pheochromocytoma PC12 cells | journal = The Journal of Biological Chemistry | volume = 277 | issue = 10 | pages = 8290–7 | date = March 2002 | pmid = 11744693 | doi = 10.1074/jbc.M108343200 | doi-access = free }}
• Src,{{cite journal | vauthors = Ahn BH, Kim SY, Kim EH, Choi KS, Kwon TK, Lee YH, Chang JS, Kim MS, Jo YH, Min DS | display-authors = 6 | title = Transmodulation between phospholipase D and c-Src enhances cell proliferation | journal = Molecular and Cellular Biology | volume = 23 | issue = 9 | pages = 3103–15 | date = May 2003 | pmid = 12697812 | pmc = 153190 | doi = 10.1128/mcb.23.9.3103-3115.2003 }} and
• Wiskott-Aldrich syndrome protein.{{cite journal | vauthors = Kantonen S, Hatton N, Mahankali M, Henkels KM, Park H, Cox D, Gomez-Cambronero J | title = A novel phospholipase D2-Grb2-WASp heterotrimer regulates leukocyte phagocytosis in a two-step mechanism | journal = Molecular and Cellular Biology | volume = 31 | issue = 22 | pages = 4524–37 | date = November 2011 | pmid = 21930784 | pmc = 3209255 | doi = 10.1128/MCB.05684-11 }}

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• N-(2-(1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)ethyl)-2-naphthamide: 75-fold selective versus PLD1, IC₅₀ = 20 nM.{{cite journal | vauthors = Lavieri RR, Scott SA, Selvy PE, Kim K, Jadhav S, Morrison RD, Daniels JS, Brown HA, Lindsley CW | display-authors = 6 | title = Design, synthesis, and biological evaluation of halogenated N-(2-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)ethyl)benzamides: discovery of an isoform-selective small molecule phospholipase D2 inhibitor | journal = Journal of Medicinal Chemistry | volume = 53 | issue = 18 | pages = 6706–19 | date = September 2010 | pmid = 20735042 | pmc = 3179181 | doi = 10.1021/jm100814g }}

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{{reflist}}

{{refbegin|35em}}

• {{cite journal | vauthors = Sundaram M, Cook HW, Byers DM | title = The MARCKS family of phospholipid binding proteins: regulation of phospholipase D and other cellular components | journal = Biochemistry and Cell Biology | volume = 82 | issue = 1 | pages = 191–200 | date = February 2004 | pmid = 15052337 | doi = 10.1139/o03-087 }}
• {{cite journal | vauthors = McDermott M, Wakelam MJ, Morris AJ | title = Phospholipase D | journal = Biochemistry and Cell Biology | volume = 82 | issue = 1 | pages = 225–53 | date = February 2004 | pmid = 15052340 | doi = 10.1139/o03-079 }}
• {{cite journal | vauthors = Colley WC, Sung TC, Roll R, Jenco J, Hammond SM, Altshuller Y, Bar-Sagi D, Morris AJ, Frohman MA | display-authors = 6 | title = Phospholipase D2, a distinct phospholipase D isoform with novel regulatory properties that provokes cytoskeletal reorganization | journal = Current Biology | volume = 7 | issue = 3 | pages = 191–201 | date = March 1997 | pmid = 9395408 | doi = 10.1016/S0960-9822(97)70090-3 | s2cid = 14008613 | doi-access = free | bibcode = 1997CBio....7..191C }}
• {{cite journal | vauthors = Steed PM, Clark KL, Boyar WC, Lasala DJ | title = Characterization of human PLD2 and the analysis of PLD isoform splice variants | journal = FASEB Journal | volume = 12 | issue = 13 | pages = 1309–17 | date = October 1998 | pmid = 9761774 | doi = 10.1096/fasebj.12.13.1309 | doi-access = free | s2cid = 27394831 }}
• {{cite journal | vauthors = Slaaby R, Jensen T, Hansen HS, Frohman MA, Seedorf K | title = PLD2 complexes with the EGF receptor and undergoes tyrosine phosphorylation at a single site upon agonist stimulation | journal = The Journal of Biological Chemistry | volume = 273 | issue = 50 | pages = 33722–7 | date = December 1998 | pmid = 9837959 | doi = 10.1074/jbc.273.50.33722 | doi-access = free }}
• {{cite journal | vauthors = Czarny M, Fiucci G, Lavie Y, Banno Y, Nozawa Y, Liscovitch M | title = Phospholipase D2: functional interaction with caveolin in low-density membrane microdomains | journal = FEBS Letters | volume = 467 | issue = 2–3 | pages = 326–32 | date = February 2000 | pmid = 10675563 | doi = 10.1016/S0014-5793(00)01174-1 | s2cid = 21891748 | doi-access = free }}
• {{cite journal | vauthors = Lee C, Kim SR, Chung JK, Frohman MA, Kilimann MW, Rhee SG | title = Inhibition of phospholipase D by amphiphysins | journal = The Journal of Biological Chemistry | volume = 275 | issue = 25 | pages = 18751–8 | date = June 2000 | pmid = 10764771 | doi = 10.1074/jbc.M001695200 | doi-access = free }}
• {{cite journal | vauthors = Park JB, Kim JH, Kim Y, Ha SH, Yoo JS, Du G, Frohman MA, Suh PG, Ryu SH | display-authors = 6 | title = Cardiac phospholipase D2 localizes to sarcolemmal membranes and is inhibited by alpha-actinin in an ADP-ribosylation factor-reversible manner | journal = The Journal of Biological Chemistry | volume = 275 | issue = 28 | pages = 21295–301 | date = July 2000 | pmid = 10801846 | doi = 10.1074/jbc.M002463200 | doi-access = free }}
• {{cite journal | vauthors = Zhang Y, Redina O, Altshuller YM, Yamazaki M, Ramos J, Chneiweiss H, Kanaho Y, Frohman MA | display-authors = 6 | title = Regulation of expression of phospholipase D1 and D2 by PEA-15, a novel protein that interacts with them | journal = The Journal of Biological Chemistry | volume = 275 | issue = 45 | pages = 35224–32 | date = November 2000 | pmid = 10926929 | doi = 10.1074/jbc.M003329200 | doi-access = free }}
• {{cite journal | vauthors = Morash SC, Byers DM, Cook HW | title = Activation of phospholipase D by PKC and GTPgammaS in human neuroblastoma cells overexpressing MARCKS | journal = Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | volume = 1487 | issue = 2–3 | pages = 177–89 | date = September 2000 | pmid = 11018470 | doi = 10.1016/s1388-1981(00)00094-9 }}
• {{cite journal | vauthors = Divecha N, Roefs M, Halstead JR, D'Andrea S, Fernandez-Borga M, Oomen L, Saqib KM, Wakelam MJ, D'Santos C | display-authors = 6 | title = Interaction of the type Ialpha PIPkinase with phospholipase D: a role for the local generation of phosphatidylinositol 4, 5-bisphosphate in the regulation of PLD2 activity | journal = The EMBO Journal | volume = 19 | issue = 20 | pages = 5440–9 | date = October 2000 | pmid = 11032811 | pmc = 314009 | doi = 10.1093/emboj/19.20.5440 }}
• {{cite journal | vauthors = Slaaby R, Du G, Altshuller YM, Frohman MA, Seedorf K | title = Insulin-induced phospholipase D1 and phospholipase D2 activity in human embryonic kidney-293 cells mediated by the phospholipase C gamma and protein kinase C alpha signalling cascade | journal = The Biochemical Journal | volume = 351 Pt 3 | issue = 3 | pages = 613–9 | date = November 2000 | pmid = 11042115 | pmc = 1221400 | doi = 10.1042/0264-6021:3510613 }}
• {{cite journal | vauthors = Hartley JL, Temple GF, Brasch MA | title = DNA cloning using in vitro site-specific recombination | journal = Genome Research | volume = 10 | issue = 11 | pages = 1788–95 | date = November 2000 | pmid = 11076863 | pmc = 310948 | doi = 10.1101/gr.143000 }}
• {{cite journal | vauthors = Lee S, Park JB, Kim JH, Kim Y, Kim JH, Shin KJ, Lee JS, Ha SH, Suh PG, Ryu SH | display-authors = 6 | title = Actin directly interacts with phospholipase D, inhibiting its activity | journal = The Journal of Biological Chemistry | volume = 276 | issue = 30 | pages = 28252–60 | date = July 2001 | pmid = 11373276 | doi = 10.1074/jbc.M008521200 | doi-access = free }}
• {{cite journal | vauthors = Sarkar S, Miwa N, Kominami H, Igarashi N, Hayashi S, Okada T, Jahangeer S, Nakamura S | display-authors = 6 | title = Regulation of mammalian phospholipase D2: interaction with and stimulation by G(M2) activator | journal = The Biochemical Journal | volume = 359 | issue = Pt 3 | pages = 599–604 | date = November 2001 | pmid = 11672434 | pmc = 1222181 | doi = 10.1042/0264-6021:3590599 }}
• {{cite journal | vauthors = Denmat-Ouisse LA, Phebidias C, Honkavaara P, Robin P, Geny B, Min DS, Bourgoin S, Frohman MA, Raymond MN | display-authors = 6 | title = Regulation of constitutive protein transit by phospholipase D in HT29-cl19A cells | journal = The Journal of Biological Chemistry | volume = 276 | issue = 52 | pages = 48840–6 | date = December 2001 | pmid = 11687572 | doi = 10.1074/jbc.M104276200 | doi-access = free }}
• {{cite journal | vauthors = Lee S, Kim JH, Lee CS, Kim JH, Kim Y, Heo K, Ihara Y, Goshima Y, Suh PG, Ryu SH | display-authors = 6 | title = Collapsin response mediator protein-2 inhibits neuronal phospholipase D(2) activity by direct interaction | journal = The Journal of Biological Chemistry | volume = 277 | issue = 8 | pages = 6542–9 | date = February 2002 | pmid = 11741937 | doi = 10.1074/jbc.M108047200 | doi-access = free }}
• {{cite journal | vauthors = Han JM, Kim JH, Lee BD, Lee SD, Kim Y, Jung YW, Lee S, Cho W, Ohba M, Kuroki T, Suh PG, Ryu SH | display-authors = 6 | title = Phosphorylation-dependent regulation of phospholipase D2 by protein kinase C delta in rat Pheochromocytoma PC12 cells | journal = The Journal of Biological Chemistry | volume = 277 | issue = 10 | pages = 8290–7 | date = March 2002 | pmid = 11744693 | doi = 10.1074/jbc.M108343200 | doi-access = free }}

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{{Esterases}}

{{Enzymes}}

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Category:EC 3.1.4