Biology:PLD2
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Short description: Protein-coding gene in the species Homo sapiens
 Generic protein structure example |
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]
Mechanism of activation
PLD2 is activated by substrate presentation.[4] 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.
Interactions
PLD2 has been shown to interact with:
- ARF1,[5][6]
- Aldolase A,[7]
- Amphiphysin,[8]
- BIN1,[8]
- Caveolin 1,[9][10]
- Glyceraldehyde 3-phosphate dehydrogenase,[11]
- PLCG1,[12]
- PRKCD,[13]
- Src,[14] and
- Wiskott-Aldrich syndrome protein.[15]
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.[16]
References
- ↑ "Assignment of human PLD2 to chromosome band 17p13.1 by fluorescence in situ hybridization". Cytogenetics and Cell Genetics 82 (3–4): 225. February 1999. doi:10.1159/000015106. PMID 9858823.
- ↑ "Cloning and initial characterization of a human phospholipase D2 (hPLD2). ADP-ribosylation factor regulates hPLD2". The Journal of Biological Chemistry 273 (21): 12846–52. May 1998. doi:10.1074/jbc.273.21.12846. PMID 9582313.
- ↑ "Entrez Gene: PLD2 phospholipase D2". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5338.
- ↑ "Kinetic disruption of lipid rafts is a mechanosensor for phospholipase D". Nature Communications 7: 13873. December 2016. doi:10.1038/ncomms13873. PMID 27976674. Bibcode: 2016NatCo...713873P.
- ↑ "Actin directly interacts with phospholipase D, inhibiting its activity". The Journal of Biological Chemistry 276 (30): 28252–60. July 2001. doi:10.1074/jbc.M008521200. PMID 11373276.
- ↑ "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. July 2000. doi:10.1074/jbc.M002463200. PMID 10801846.
- ↑ "Phospholipase D2 directly interacts with aldolase via Its PH domain". Biochemistry 41 (10): 3414–21. March 2002. doi:10.1021/bi015700a. PMID 11876650.
- ↑ 8.0 8.1 "Inhibition of phospholipase D by amphiphysins". The Journal of Biological Chemistry 275 (25): 18751–8. June 2000. doi:10.1074/jbc.M001695200. PMID 10764771.
- ↑ "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. December 2003. doi:10.1111/j.1523-1747.2003.12614.x. PMID 14675200.
- ↑ "Phospholipase D2: functional interaction with caveolin in low-density membrane microdomains". FEBS Letters 467 (2–3): 326–32. February 2000. doi:10.1016/s0014-5793(00)01174-1. PMID 10675563.
- ↑ "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. June 2003. doi:10.1046/j.1471-4159.2003.01755.x. PMID 12753082.
- ↑ "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. May 2003. doi:10.1074/jbc.M208438200. PMID 12646582.
- ↑ "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. March 2002. doi:10.1074/jbc.M108343200. PMID 11744693.
- ↑ "Transmodulation between phospholipase D and c-Src enhances cell proliferation". Molecular and Cellular Biology 23 (9): 3103–15. May 2003. doi:10.1128/mcb.23.9.3103-3115.2003. PMID 12697812.
- ↑ "A novel phospholipase D2-Grb2-WASp heterotrimer regulates leukocyte phagocytosis in a two-step mechanism". Molecular and Cellular Biology 31 (22): 4524–37. November 2011. doi:10.1128/MCB.05684-11. PMID 21930784.
- ↑ "Design, synthesis, and biological evaluation of halogenated N-(2-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5decan-8-yl)ethyl)benzamides: discovery of an isoform-selective small molecule phospholipase D2 inhibitor"]. Journal of Medicinal Chemistry 53 (18): 6706–19. September 2010. doi:10.1021/jm100814g. PMID 20735042.
Further reading
- "The MARCKS family of phospholipid binding proteins: regulation of phospholipase D and other cellular components". Biochemistry and Cell Biology 82 (1): 191–200. February 2004. doi:10.1139/o03-087. PMID 15052337.
- "Phospholipase D". Biochemistry and Cell Biology 82 (1): 225–53. February 2004. doi:10.1139/o03-079. PMID 15052340.
- "Phospholipase D2, a distinct phospholipase D isoform with novel regulatory properties that provokes cytoskeletal reorganization". Current Biology 7 (3): 191–201. March 1997. doi:10.1016/S0960-9822(97)70090-3. PMID 9395408.
- "Characterization of human PLD2 and the analysis of PLD isoform splice variants". FASEB Journal 12 (13): 1309–17. October 1998. doi:10.1096/fasebj.12.13.1309. PMID 9761774.
- "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. December 1998. doi:10.1074/jbc.273.50.33722. PMID 9837959.
- "Phospholipase D2: functional interaction with caveolin in low-density membrane microdomains". FEBS Letters 467 (2–3): 326–32. February 2000. doi:10.1016/S0014-5793(00)01174-1. PMID 10675563.
- "Inhibition of phospholipase D by amphiphysins". The Journal of Biological Chemistry 275 (25): 18751–8. June 2000. doi:10.1074/jbc.M001695200. PMID 10764771.
- "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. July 2000. doi:10.1074/jbc.M002463200. PMID 10801846.
- "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. November 2000. doi:10.1074/jbc.M003329200. PMID 10926929.
- "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. September 2000. doi:10.1016/s1388-1981(00)00094-9. PMID 11018470.
- "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. October 2000. doi:10.1093/emboj/19.20.5440. PMID 11032811.
- "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. November 2000. doi:10.1042/0264-6021:3510613. PMID 11042115.
- "DNA cloning using in vitro site-specific recombination". Genome Research 10 (11): 1788–95. November 2000. doi:10.1101/gr.143000. PMID 11076863.
- "Actin directly interacts with phospholipase D, inhibiting its activity". The Journal of Biological Chemistry 276 (30): 28252–60. July 2001. doi:10.1074/jbc.M008521200. PMID 11373276.
- "Regulation of mammalian phospholipase D2: interaction with and stimulation by G(M2) activator". The Biochemical Journal 359 (Pt 3): 599–604. November 2001. doi:10.1042/0264-6021:3590599. PMID 11672434.
- "Regulation of constitutive protein transit by phospholipase D in HT29-cl19A cells". The Journal of Biological Chemistry 276 (52): 48840–6. December 2001. doi:10.1074/jbc.M104276200. PMID 11687572.
- "Collapsin response mediator protein-2 inhibits neuronal phospholipase D(2) activity by direct interaction". The Journal of Biological Chemistry 277 (8): 6542–9. February 2002. doi:10.1074/jbc.M108047200. PMID 11741937.
- "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. March 2002. doi:10.1074/jbc.M108343200. PMID 11744693.
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