Protein-coding gene in the species Homo sapiens
Phospholipase D2 is an enzyme that in humans is encoded by the PLD2 gene .[5] [6]
Function [ edit ] 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][7]
Mechanism of activation [ edit ] PLD2 is activated by substrate presentation .[8]
Interactions [ edit ] PLD2 has been shown to interact with:
Inhibitors [ edit ] 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.[20]
References [ edit ]
^ a b c GRCh38: Ensembl release 89: ENSG00000129219 – Ensembl , May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020828 – Ensembl , May 2017^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ Park SH, Ryu SH, Suh PG, Kim H (February 1999). "Assignment of human PLD2 to chromosome band 17p13.1 by fluorescence in situ hybridization". Cytogenetics and Cell Genetics . 82 (3–4): 225. doi :10.1159/000015106 . PMID 9858823 . S2CID 46805227 . ^ Lopez I, Arnold RS, Lambeth JD (May 1998). "Cloning and initial characterization of a human phospholipase D2 (hPLD2). ADP-ribosylation factor regulates hPLD2" . The Journal of Biological Chemistry . 273 (21): 12846–52. doi :10.1074/jbc.273.21.12846 PMID 9582313 . ^ "Entrez Gene: PLD2 phospholipase D2" .^ Petersen EN, Chung HW, Nayebosadri A, Hansen SB (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 . ^ Lee S, Park JB, Kim JH, Kim Y, Kim JH, Shin KJ, et al. (July 2001). "Actin directly interacts with phospholipase D, inhibiting its activity" . The Journal of Biological Chemistry . 276 (30): 28252–60. doi :10.1074/jbc.M008521200 PMID 11373276 . ^ Park JB, Kim JH, Kim Y, Ha SH, Yoo JS, Du G, et al. (July 2000). "Cardiac phospholipase D2 localizes to sarcolemmal membranes and is inhibited by alpha-actinin in an ADP-ribosylation factor-reversible manner" . The Journal of Biological Chemistry . 275 (28): 21295–301. doi :10.1074/jbc.M002463200 PMID 10801846 . ^ Kim JH, Lee S, Kim JH, Lee TG, Hirata M, Suh PG, Ryu SH (March 2002). "Phospholipase D2 directly interacts with aldolase via Its PH domain". Biochemistry . 41 (10): 3414–21. doi :10.1021/bi015700a . PMID 11876650 . ^ a b Lee C, Kim SR, Chung JK, Frohman MA, Kilimann MW, Rhee SG (June 2000). "Inhibition of phospholipase D by amphiphysins" . The Journal of Biological Chemistry . 275 (25): 18751–8. doi :10.1074/jbc.M001695200 PMID 10764771 . ^ Zheng X, Bollinger Bollag W (December 2003). "Aquaporin 3 colocates with phospholipase d2 in caveolin-rich membrane microdomains and is downregulated upon keratinocyte differentiation" . The Journal of Investigative Dermatology . 121 (6): 1487–95. doi :10.1111/j.1523-1747.2003.12614.x PMID 14675200 . ^ Czarny M, Fiucci G, Lavie Y, Banno Y, Nozawa Y, Liscovitch M (February 2000). "Phospholipase D2: functional interaction with caveolin in low-density membrane microdomains" . FEBS Letters . 467 (2–3): 326–32. doi :10.1016/s0014-5793(00)01174-1 PMID 10675563 . S2CID 21891748 . ^ Kim JH, Lee S, Park JB, Lee SD, Kim JH, Ha SH, et al. (June 2003). "Hydrogen peroxide induces association between glyceraldehyde 3-phosphate dehydrogenase and phospholipase D2 to facilitate phospholipase D2 activation in PC12 cells". Journal of Neurochemistry . 85 (5): 1228–36. doi :10.1046/j.1471-4159.2003.01755.x . PMID 12753082 . S2CID 27513985 . ^ Jang IH, Lee S, Park JB, Kim JH, Lee CS, Hur EM, et al. (May 2003). "The direct interaction of phospholipase C-gamma 1 with phospholipase D2 is important for epidermal growth factor signaling" . The Journal of Biological Chemistry . 278 (20): 18184–90. doi :10.1074/jbc.M208438200 PMID 12646582 . ^ Han JM, Kim JH, Lee BD, Lee SD, Kim Y, Jung YW, et al. (March 2002). "Phosphorylation-dependent regulation of phospholipase D2 by protein kinase C delta in rat Pheochromocytoma PC12 cells" . The Journal of Biological Chemistry . 277 (10): 8290–7. doi :10.1074/jbc.M108343200 PMID 11744693 . ^ Ahn BH, Kim SY, Kim EH, Choi KS, Kwon TK, Lee YH, et al. (May 2003). "Transmodulation between phospholipase D and c-Src enhances cell proliferation" . Molecular and Cellular Biology . 23 (9): 3103–15. doi :10.1128/mcb.23.9.3103-3115.2003 . PMC 153190 PMID 12697812 . ^ Kantonen S, Hatton N, Mahankali M, Henkels KM, Park H, Cox D, Gomez-Cambronero J (November 2011). "A novel phospholipase D2-Grb2-WASp heterotrimer regulates leukocyte phagocytosis in a two-step mechanism" . Molecular and Cellular Biology . 31 (22): 4524–37. doi :10.1128/MCB.05684-11 . PMC 3209255 PMID 21930784 . ^ Lavieri RR, Scott SA, Selvy PE, Kim K, Jadhav S, Morrison RD, et al. (September 2010). "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 of Medicinal Chemistry . 53 (18): 6706–19. doi :10.1021/jm100814g . PMC 3179181 PMID 20735042 .
Further reading [ edit ]
Sundaram M, Cook HW, Byers DM (February 2004). "The MARCKS family of phospholipid binding proteins: regulation of phospholipase D and other cellular components". Biochemistry and Cell Biology . 82 (1): 191–200. doi :10.1139/o03-087 . PMID 15052337 . McDermott M, Wakelam MJ, Morris AJ (February 2004). "Phospholipase D". Biochemistry and Cell Biology . 82 (1): 225–53. doi :10.1139/o03-079 . PMID 15052340 . Colley WC, Sung TC, Roll R, Jenco J, Hammond SM, Altshuller Y, et al. (March 1997). "Phospholipase D2, a distinct phospholipase D isoform with novel regulatory properties that provokes cytoskeletal reorganization" . Current Biology . 7 (3): 191–201. Bibcode :1997CBio....7..191C . doi :10.1016/S0960-9822(97)70090-3 PMID 9395408 . S2CID 14008613 . Steed PM, Clark KL, Boyar WC, Lasala DJ (October 1998). "Characterization of human PLD2 and the analysis of PLD isoform splice variants" . FASEB Journal . 12 (13): 1309–17. doi :10.1096/fasebj.12.13.1309 PMID 9761774 . S2CID 27394831 . Slaaby R, Jensen T, Hansen HS, Frohman MA, Seedorf K (December 1998). "PLD2 complexes with the EGF receptor and undergoes tyrosine phosphorylation at a single site upon agonist stimulation" . The Journal of Biological Chemistry . 273 (50): 33722–7. doi :10.1074/jbc.273.50.33722 PMID 9837959 . Czarny M, Fiucci G, Lavie Y, Banno Y, Nozawa Y, Liscovitch M (February 2000). "Phospholipase D2: functional interaction with caveolin in low-density membrane microdomains" . FEBS Letters . 467 (2–3): 326–32. doi :10.1016/S0014-5793(00)01174-1 PMID 10675563 . S2CID 21891748 . Lee C, Kim SR, Chung JK, Frohman MA, Kilimann MW, Rhee SG (June 2000). "Inhibition of phospholipase D by amphiphysins" . The Journal of Biological Chemistry . 275 (25): 18751–8. doi :10.1074/jbc.M001695200 PMID 10764771 . Park JB, Kim JH, Kim Y, Ha SH, Yoo JS, Du G, et al. (July 2000). "Cardiac phospholipase D2 localizes to sarcolemmal membranes and is inhibited by alpha-actinin in an ADP-ribosylation factor-reversible manner" . The Journal of Biological Chemistry . 275 (28): 21295–301. doi :10.1074/jbc.M002463200 PMID 10801846 . Zhang Y, Redina O, Altshuller YM, Yamazaki M, Ramos J, Chneiweiss H, et al. (November 2000). "Regulation of expression of phospholipase D1 and D2 by PEA-15, a novel protein that interacts with them" . The Journal of Biological Chemistry . 275 (45): 35224–32. doi :10.1074/jbc.M003329200 PMID 10926929 . Morash SC, Byers DM, Cook HW (September 2000). "Activation of phospholipase D by PKC and GTPgammaS in human neuroblastoma cells overexpressing MARCKS". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids . 1487 (2–3): 177–89. doi :10.1016/s1388-1981(00)00094-9 . PMID 11018470 . Divecha N, Roefs M, Halstead JR, D'Andrea S, Fernandez-Borga M, Oomen L, et al. (October 2000). "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" . The EMBO Journal . 19 (20): 5440–9. doi :10.1093/emboj/19.20.5440 . PMC 314009 PMID 11032811 . Slaaby R, Du G, Altshuller YM, Frohman MA, Seedorf K (November 2000). "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" . The Biochemical Journal . 351 Pt 3 (3): 613–9. doi :10.1042/0264-6021:3510613 . PMC 1221400 PMID 11042115 . Hartley JL, Temple GF, Brasch MA (November 2000). "DNA cloning using in vitro site-specific recombination" . Genome Research . 10 (11): 1788–95. doi :10.1101/gr.143000 . PMC 310948 PMID 11076863 . Lee S, Park JB, Kim JH, Kim Y, Kim JH, Shin KJ, et al. (July 2001). "Actin directly interacts with phospholipase D, inhibiting its activity" . The Journal of Biological Chemistry . 276 (30): 28252–60. doi :10.1074/jbc.M008521200 PMID 11373276 . Sarkar S, Miwa N, Kominami H, Igarashi N, Hayashi S, Okada T, et al. (November 2001). "Regulation of mammalian phospholipase D2: interaction with and stimulation by G(M2) activator" . The Biochemical Journal . 359 (Pt 3): 599–604. doi :10.1042/0264-6021:3590599 . PMC 1222181 PMID 11672434 . Denmat-Ouisse LA, Phebidias C, Honkavaara P, Robin P, Geny B, Min DS, et al. (December 2001). "Regulation of constitutive protein transit by phospholipase D in HT29-cl19A cells" . The Journal of Biological Chemistry . 276 (52): 48840–6. doi :10.1074/jbc.M104276200 PMID 11687572 . Lee S, Kim JH, Lee CS, Kim JH, Kim Y, Heo K, et al. (February 2002). "Collapsin response mediator protein-2 inhibits neuronal phospholipase D(2) activity by direct interaction" . The Journal of Biological Chemistry . 277 (8): 6542–9. doi :10.1074/jbc.M108047200 PMID 11741937 . Han JM, Kim JH, Lee BD, Lee SD, Kim Y, Jung YW, et al. (March 2002). "Phosphorylation-dependent regulation of phospholipase D2 by protein kinase C delta in rat Pheochromocytoma PC12 cells" . The Journal of Biological Chemistry . 277 (10): 8290–7. doi :10.1074/jbc.M108343200 PMID 11744693 .
Activity Regulation Classification Kinetics Types
