PLD2

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Identifiers
Aliases
External IDs	GeneCards: [1]
Orthologs
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	Wikidata
View/Edit Human

Phospholipase D2 is an enzyme that in humans is encoded by the PLD2 gene.^[1]^[2]

Function

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]^[3]

Interactions

PLD2 has been shown to interact with:

ARF1,^[4]^[5]
Aldolase A,^[6]
Amphiphysin,^[7]
BIN1,^[7]
Caveolin 1,^[8]^[9]
Glyceraldehyde 3-phosphate dehydrogenase,^[10]
PLCG1,^[11]
PRKCD,^[12]
Src,^[13] and
Wiskott-Aldrich syndrome protein.^[14]

Inhibitors

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.^[15]

References

↑ Park SH, Ryu SH, Suh PG, Kim H (February 1999). "Assignment of human PLD2 to chromosome band 17p13.1 by fluorescence in situ hybridization". Cytogenet Cell Genet. 82 (3–4): 225. doi:10.1159/000015106. PMID 9858823.
↑ Lopez I, Arnold RS, Lambeth JD (June 1998). "Cloning and initial characterization of a human phospholipase D2 (hPLD2). ADP-ribosylation factor regulates hPLD2". J Biol Chem. 273 (21): 12846–52. doi:10.1074/jbc.273.21.12846. PMID 9582313.
↑ "Entrez Gene: PLD2 phospholipase D2".
↑ Lee S, Park JB, Kim JH, Kim Y, Kim JH, Shin KJ, Lee JS, Ha SH, Suh PG, Ryu SH (July 2001). "Actin directly interacts with phospholipase D, inhibiting its activity". J. Biol. Chem. 276 (30): 28252–60. doi:10.1074/jbc.M008521200. PMID 11373276.
↑ Park JB, Kim JH, Kim Y, Ha SH, Yoo JS, Du G, Frohman MA, Suh PG, Ryu SH (July 2000). "Cardiac phospholipase D2 localizes to sarcolemmal membranes and is inhibited by alpha-actinin in an ADP-ribosylation factor-reversible manner". J. Biol. Chem. 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.
↑ ^7.0 ^7.1 Lee C, Kim SR, Chung JK, Frohman MA, Kilimann MW, Rhee SG (June 2000). "Inhibition of phospholipase D by amphiphysins". J. Biol. Chem. 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". J. Invest. Dermatol. 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 Lett. 467 (2–3): 326–32. doi:10.1016/s0014-5793(00)01174-1. PMID 10675563.
↑ Kim JH, Lee S, Park JB, Lee SD, Kim JH, Ha SH, Hasumi K, Endo A, Suh PG, Ryu SH (June 2003). "Hydrogen peroxide induces association between glyceraldehyde 3-phosphate dehydrogenase and phospholipase D2 to facilitate phospholipase D2 activation in PC12 cells". J. Neurochem. 85 (5): 1228–36. doi:10.1046/j.1471-4159.2003.01755.x. PMID 12753082.
↑ Jang IH, Lee S, Park JB, Kim JH, Lee CS, Hur EM, Kim IS, Kim KT, Yagisawa H, Suh PG, Ryu SH (May 2003). "The direct interaction of phospholipase C-gamma 1 with phospholipase D2 is important for epidermal growth factor signaling". J. Biol. Chem. 278 (20): 18184–90. doi:10.1074/jbc.M208438200. PMID 12646582.
↑ Han JM, Kim JH, Lee BD, Lee SD, Kim Y, Jung YW, Lee S, Cho W, Ohba M, Kuroki T, Suh PG, Ryu SH (March 2002). "Phosphorylation-dependent regulation of phospholipase D2 by protein kinase C delta in rat Pheochromocytoma PC12 cells". J. Biol. Chem. 277 (10): 8290–7. doi:10.1074/jbc.M108343200. PMID 11744693.
↑ Ahn BH, Kim SY, Kim EH, Choi KS, Kwon TK, Lee YH, Chang JS, Kim MS, Jo YH, Min DS (May 2003). "Transmodulation between phospholipase D and c-Src enhances cell proliferation". Mol. Cell. Biol. 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". Mol. Cell. Biol. 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, Daniels JS, Brown HA, Lindsley CW (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". J. Med. Chem. 53 (18): 6706–19. doi:10.1021/jm100814g. PMC 3179181. PMID 20735042.

Sundaram M, Cook HW, Byers DM (2004). "The MARCKS family of phospholipid binding proteins: regulation of phospholipase D and other cellular components". Biochem. Cell Biol. 82 (1): 191–200. doi:10.1139/o03-087. PMID 15052337.
McDermott M, Wakelam MJ, Morris AJ (2004). "Phospholipase D". Biochem. Cell Biol. 82 (1): 225–53. doi:10.1139/o03-079. PMID 15052340.
Colley WC, Sung TC, Roll R, Jenco J, Hammond SM, Altshuller Y, Bar-Sagi D, Morris AJ, Frohman MA (1997). "Phospholipase D2, a distinct phospholipase D isoform with novel regulatory properties that provokes cytoskeletal reorganization". Curr. Biol. 7 (3): 191–201. doi:10.1016/S0960-9822(97)70090-3. PMID 9395408.
Steed PM, Clark KL, Boyar WC, Lasala DJ (1998). "Characterization of human PLD2 and the analysis of PLD isoform splice variants". FASEB J. 12 (13): 1309–17. PMID 9761774.
Slaaby R, Jensen T, Hansen HS, Frohman MA, Seedorf K (1999). "PLD2 complexes with the EGF receptor and undergoes tyrosine phosphorylation at a single site upon agonist stimulation". J. Biol. Chem. 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 (2000). "Phospholipase D2: functional interaction with caveolin in low-density membrane microdomains". FEBS Lett. 467 (2–3): 326–32. doi:10.1016/S0014-5793(00)01174-1. PMID 10675563.
Lee C, Kim SR, Chung JK, Frohman MA, Kilimann MW, Rhee SG (2000). "Inhibition of phospholipase D by amphiphysins". J. Biol. Chem. 275 (25): 18751–8. doi:10.1074/jbc.M001695200. PMID 10764771.
Park JB, Kim JH, Kim Y, Ha SH, Yoo JS, Du G, Frohman MA, Suh PG, Ryu SH (2000). "Cardiac phospholipase D2 localizes to sarcolemmal membranes and is inhibited by alpha-actinin in an ADP-ribosylation factor-reversible manner". J. Biol. Chem. 275 (28): 21295–301. doi:10.1074/jbc.M002463200. PMID 10801846.
Zhang Y, Redina O, Altshuller YM, Yamazaki M, Ramos J, Chneiweiss H, Kanaho Y, Frohman MA (2001). "Regulation of expression of phospholipase D1 and D2 by PEA-15, a novel protein that interacts with them". J. Biol. Chem. 275 (45): 35224–32. doi:10.1074/jbc.M003329200. PMID 10926929.
Morash SC, Byers DM, Cook HW (2000). "Activation of phospholipase D by PKC and GTPgammaS in human neuroblastoma cells overexpressing MARCKS". Biochim. Biophys. Acta. 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, Saqib KM, Wakelam MJ, D'Santos C (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". EMBO J. 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 (2001). "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". Biochem. J. 351 (3): 613–9. doi:10.1042/0264-6021:3510613. PMC 1221400. PMID 11042115.
Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination". Genome Res. 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, Lee JS, Ha SH, Suh PG, Ryu SH (2001). "Actin directly interacts with phospholipase D, inhibiting its activity". J. Biol. Chem. 276 (30): 28252–60. doi:10.1074/jbc.M008521200. PMID 11373276.
Sarkar S, Miwa N, Kominami H, Igarashi N, Hayashi S, Okada T, Jahangeer S, Nakamura S (2001). "Regulation of mammalian phospholipase D2: interaction with and stimulation by G(M2) activator". Biochem. J. 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, Bourgoin S, Frohman MA, Raymond MN (2002). "Regulation of constitutive protein transit by phospholipase D in HT29-cl19A cells". J. Biol. Chem. 276 (52): 48840–6. doi:10.1074/jbc.M104276200. PMID 11687572.
Lee S, Kim JH, Lee CS, Kim JH, Kim Y, Heo K, Ihara Y, Goshima Y, Suh PG, Ryu SH (2002). "Collapsin response mediator protein-2 inhibits neuronal phospholipase D(2) activity by direct interaction". J. Biol. Chem. 277 (8): 6542–9. doi:10.1074/jbc.M108047200. PMID 11741937.
Han JM, Kim JH, Lee BD, Lee SD, Kim Y, Jung YW, Lee S, Cho W, Ohba M, Kuroki T, Suh PG, Ryu SH (2002). "Phosphorylation-dependent regulation of phospholipase D2 by protein kinase C delta in rat Pheochromocytoma PC12 cells". J. Biol. Chem. 277 (10): 8290–7. doi:10.1074/jbc.M108343200. PMID 11744693.

[pmid9858823-1] Park SH, Ryu SH, Suh PG, Kim H (February 1999). "Assignment of human PLD2 to chromosome band 17p13.1 by fluorescence in situ hybridization". Cytogenet Cell Genet. 82 (3–4): 225. doi:10.1159/000015106. PMID 9858823.

[pmid9582313-2] Lopez I, Arnold RS, Lambeth JD (June 1998). "Cloning and initial characterization of a human phospholipase D2 (hPLD2). ADP-ribosylation factor regulates hPLD2". J Biol Chem. 273 (21): 12846–52. doi:10.1074/jbc.273.21.12846. PMID 9582313.

[entrez-3] "Entrez Gene: PLD2 phospholipase D2".

[pmid11373276-4] Lee S, Park JB, Kim JH, Kim Y, Kim JH, Shin KJ, Lee JS, Ha SH, Suh PG, Ryu SH (July 2001). "Actin directly interacts with phospholipase D, inhibiting its activity". J. Biol. Chem. 276 (30): 28252–60. doi:10.1074/jbc.M008521200. PMID 11373276.

[pmid10801846-5] Park JB, Kim JH, Kim Y, Ha SH, Yoo JS, Du G, Frohman MA, Suh PG, Ryu SH (July 2000). "Cardiac phospholipase D2 localizes to sarcolemmal membranes and is inhibited by alpha-actinin in an ADP-ribosylation factor-reversible manner". J. Biol. Chem. 275 (28): 21295–301. doi:10.1074/jbc.M002463200. PMID 10801846.

[pmid11876650-6] 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.

[pmid10764771-7] 7.0 ^7.1 Lee C, Kim SR, Chung JK, Frohman MA, Kilimann MW, Rhee SG (June 2000). "Inhibition of phospholipase D by amphiphysins". J. Biol. Chem. 275 (25): 18751–8. doi:10.1074/jbc.M001695200. PMID 10764771.

[pmid14675200-8] Zheng X, Bollinger Bollag W (December 2003). "Aquaporin 3 colocates with phospholipase d2 in caveolin-rich membrane microdomains and is downregulated upon keratinocyte differentiation". J. Invest. Dermatol. 121 (6): 1487–95. doi:10.1111/j.1523-1747.2003.12614.x. PMID 14675200.

[pmid10675563-9] 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 Lett. 467 (2–3): 326–32. doi:10.1016/s0014-5793(00)01174-1. PMID 10675563.

[pmid12753082-10] Kim JH, Lee S, Park JB, Lee SD, Kim JH, Ha SH, Hasumi K, Endo A, Suh PG, Ryu SH (June 2003). "Hydrogen peroxide induces association between glyceraldehyde 3-phosphate dehydrogenase and phospholipase D2 to facilitate phospholipase D2 activation in PC12 cells". J. Neurochem. 85 (5): 1228–36. doi:10.1046/j.1471-4159.2003.01755.x. PMID 12753082.

[pmid12646582-11] Jang IH, Lee S, Park JB, Kim JH, Lee CS, Hur EM, Kim IS, Kim KT, Yagisawa H, Suh PG, Ryu SH (May 2003). "The direct interaction of phospholipase C-gamma 1 with phospholipase D2 is important for epidermal growth factor signaling". J. Biol. Chem. 278 (20): 18184–90. doi:10.1074/jbc.M208438200. PMID 12646582.

[pmid11744693-12] Han JM, Kim JH, Lee BD, Lee SD, Kim Y, Jung YW, Lee S, Cho W, Ohba M, Kuroki T, Suh PG, Ryu SH (March 2002). "Phosphorylation-dependent regulation of phospholipase D2 by protein kinase C delta in rat Pheochromocytoma PC12 cells". J. Biol. Chem. 277 (10): 8290–7. doi:10.1074/jbc.M108343200. PMID 11744693.

[pmid12697812-13] Ahn BH, Kim SY, Kim EH, Choi KS, Kwon TK, Lee YH, Chang JS, Kim MS, Jo YH, Min DS (May 2003). "Transmodulation between phospholipase D and c-Src enhances cell proliferation". Mol. Cell. Biol. 23 (9): 3103–15. doi:10.1128/mcb.23.9.3103-3115.2003. PMC 153190. PMID 12697812.

[pmid21930784-14] 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". Mol. Cell. Biol. 31 (22): 4524–37. doi:10.1128/MCB.05684-11. PMC 3209255. PMID 21930784.

[pmid20735042-15] Lavieri RR, Scott SA, Selvy PE, Kim K, Jadhav S, Morrison RD, Daniels JS, Brown HA, Lindsley CW (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". J. Med. Chem. 53 (18): 6706–19. doi:10.1021/jm100814g. PMC 3179181. PMID 20735042.

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v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list)

PLD2

Contents

Function

Interactions

Inhibitors

References

Further reading

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PLD2

Function

Interactions

Inhibitors

References

Further reading

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