Phospholipase D1

Phospholipase D1, phosphatidylcholine-specific
Identifiers
Symbols	PLD1;
External IDs	OMIM: 602382 MGI: 109585 HomoloGene: 116234 GeneCards: PLD1 Gene
EC number	3.1.4.4
Gene Ontology Molecular function • phospholipase D activity • hydrolase activity • phosphatidylinositol binding • NAPE-specific phospholipase D activity Cellular component • Golgi membrane • cytoplasm • endosome • endoplasmic reticulum • endoplasmic reticulum membrane • microsome • Golgi apparatus • membrane • lamellipodium • late endosome membrane • vesicle • Golgi cisterna • perinuclear region of cytoplasm Biological process • phosphatidic acid biosynthetic process • chemotaxis • cell communication • small GTPase mediated signal transduction • Ras protein signal transduction • phospholipid biosynthetic process • phospholipid catabolic process • lipid catabolic process • positive regulation of cell migration • response to peptide hormone stimulus • defense response to Gram-positive bacterium Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5337	18805
Ensembl	ENSG00000075651	ENSMUSG00000027695
UniProt	Q13393	Q9Z280
RefSeq (mRNA)	NM_001130081.1	NM_008875
RefSeq (protein)	NP_001123553.1	NP_032901
Location (UCSC)	Chr 3: 171.32 – 171.53 Mb	Chr 3: 27.84 – 28.03 Mb
PubMed search	[1]	[2]

Phospholipase D1 is an enzyme that in humans is encoded by the PLD1 gene.^[1][2]

Phosphatidylcholine (PC)-specific phospholipases D (PLDs) EC 3.1.4.4 catalyze the hydrolysis of PC to produce phosphatidic acid and choline. A range of agonists acting through G protein-coupled receptors and receptor tyrosine kinases stimulate this hydrolysis. PC-specific PLD activity has been implicated in numerous cellular pathways, including signal transduction, membrane trafficking, and the regulation of mitosis (Hammond et al., 1995).[supplied by OMIM]^[3]

Interactions

Phospholipase D1 has been shown to interact with RALA,^[4][5] BIN1,^[6] Amphiphysin,^[6] Alpha-synuclein,^[7] PEA15,^[8] RHOA,^[9][10] Protein kinase N1^[11] and CDC42.^[12]

Inhibitors

• VU-0359595: 1,700-fold selective versus phospholipase D2, IC₅₀ = 3.7nM.^[13]

References

1. ^ Park SH, Chun YH, Ryu SH, Suh PG, Kim H (Feb 1999). "Assignment of human PLD1 to human chromosome band 3q26 by fluorescence in situ hybridization". Cytogenet Cell Genet 82 (3-4): 224. doi:10.1159/000015105. PMID 9858822. 
2. ^ Hammond SM, Altshuller YM, Sung TC, Rudge SA, Rose K, Engebrecht J, Morris AJ, Frohman MA (Jan 1996). "Human ADP-ribosylation factor-activated phosphatidylcholine-specific phospholipase D defines a new and highly conserved gene family". J Biol Chem 270 (50): 29640–3. doi:10.1074/jbc.270.50.29640. PMID 8530346. 
3. ^ "Entrez Gene: PLD1 phospholipase D1, phosphatidylcholine-specific". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5337. 
4. ^ Luo, J Q; Liu X, Hammond S M, Colley W C, Feig L A, Frohman M A, Morris A J, Foster D A (Jun. 1997). "RalA interacts directly with the Arf-responsive, PIP2-dependent phospholipase D1". Biochem. Biophys. Res. Commun. (UNITED STATES) 235 (3): 854–9. doi:10.1006/bbrc.1997.6793. ISSN 0006-291X. PMID 9207251. 
5. ^ Kim, J H; Lee S D, Han J M, Lee T G, Kim Y, Park J B, Lambeth J D, Suh P G, Ryu S H (Jul. 1998). "Activation of phospholipase D1 by direct interaction with ADP-ribosylation factor 1 and RalA". FEBS Lett. (NETHERLANDS) 430 (3): 231–5. doi:10.1016/S0014-5793(98)00661-9. ISSN 0014-5793. PMID 9688545. 
6. ^ ^{a b} Lee, C; Kim S R, Chung J K, Frohman M A, Kilimann M W, Rhee S G (Jun. 2000). "Inhibition of phospholipase D by amphiphysins". J. Biol. Chem. (UNITED STATES) 275 (25): 18751–8. doi:10.1074/jbc.M001695200. ISSN 0021-9258. PMID 10764771. 
7. ^ Ahn, Bong-Hyun; Rhim Hyangshuk, Kim Shi Yeon, Sung Young-Mo, Lee Mun-Yong, Choi Ju-Youn, Wolozin Benjamin, Chang Jong-Soo, Lee Young Han, Kwon Taeg Kyu, Chung Kwang Chul, Yoon Shin-Hee, Hahn Sang June, Kim Myung-Suk, Jo Yang-Hyeok, Min Do Sik (Apr. 2002). "alpha-Synuclein interacts with phospholipase D isozymes and inhibits pervanadate-induced phospholipase D activation in human embryonic kidney-293 cells". J. Biol. Chem. (United States) 277 (14): 12334–42. doi:10.1074/jbc.M110414200. ISSN 0021-9258. PMID 11821392. 
8. ^ Zhang, Y; Redina O, Altshuller Y M, Yamazaki M, Ramos J, Chneiweiss H, Kanaho Y, Frohman M A (Nov. 2000). "Regulation of expression of phospholipase D1 and D2 by PEA-15, a novel protein that interacts with them". J. Biol. Chem. (UNITED STATES) 275 (45): 35224–32. doi:10.1074/jbc.M003329200. ISSN 0021-9258. PMID 10926929. 
9. ^ Genth, Harald; Schmidt Martina, Gerhard Ralf, Aktories Klaus, Just Ingo (Feb. 2003). "Activation of phospholipase D1 by ADP-ribosylated RhoA". Biochem. Biophys. Res. Commun. (United States) 302 (1): 127–32. doi:10.1016/S0006-291X(03)00112-8. ISSN 0006-291X. PMID 12593858. 
10. ^ Cai, S; Exton J H (May. 2001). "Determination of interaction sites of phospholipase D1 for RhoA". Biochem. J. (England) 355 (Pt 3): 779–85. ISSN 0264-6021. PMC 1221795. PMID 11311142. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1221795. 
11. ^ Oishi, K; Takahashi M, Mukai H, Banno Y, Nakashima S, Kanaho Y, Nozawa Y, Ono Y (May. 2001). "PKN regulates phospholipase D1 through direct interaction". J. Biol. Chem. (United States) 276 (21): 18096–101. doi:10.1074/jbc.M010646200. ISSN 0021-9258. PMID 11259428. 
12. ^ Walker, S J; Wu W J, Cerione R A, Brown H A (May. 2000). "Activation of phospholipase D1 by Cdc42 requires the Rho insert region". J. Biol. Chem. (UNITED STATES) 275 (21): 15665–8. doi:10.1074/jbc.M000076200. ISSN 0021-9258. PMID 10747870. 
13. ^ Lewis JA, Scott SA, Lavieri R, Buck JR, Selvy PE, Stoops SL, Armstrong MD, Brown HA, Lindsley CW (April 2009). "Design and synthesis of isoform-selective phospholipase D (PLD) inhibitors. Part I: Impact of alternative halogenated privileged structures for PLD1 specificity". Bioorg. Med. Chem. Lett. 19 (7): 1916–20. doi:10.1016/j.bmcl.2009.02.057. PMID 19268584. 

Further reading

• Hammond SM, Jenco JM, Nakashima S, et al. (1997). "Characterization of two alternately spliced forms of phospholipase D1. Activation of the purified enzymes by phosphatidylinositol 4,5-bisphosphate, ADP-ribosylation factor, and Rho family monomeric GTP-binding proteins and protein kinase C-alpha.". J. Biol. Chem. 272 (6): 3860–8. doi:10.1074/jbc.272.6.3860. PMID 9013646. 
• Luo JQ, Liu X, Hammond SM, et al. (1997). "RalA interacts directly with the Arf-responsive, PIP2-dependent phospholipase D1.". Biochem. Biophys. Res. Commun. 235 (3): 854–9. doi:10.1006/bbrc.1997.6793. PMID 9207251. 
• Colley WC, Sung TC, Roll R, et al. (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. 
• Bae CD, Min DS, Fleming IN, Exton JH (1998). "Determination of interaction sites on the small G protein RhoA for phospholipase D.". J. Biol. Chem. 273 (19): 11596–604. doi:10.1074/jbc.273.19.11596. PMID 9565577. 
• Lopez I, Arnold RS, Lambeth JD (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. 
• Kim JH, Lee SD, Han JM, et al. (1998). "Activation of phospholipase D1 by direct interaction with ADP-ribosylation factor 1 and RalA.". FEBS Lett. 430 (3): 231–5. doi:10.1016/S0014-5793(98)00661-9. PMID 9688545. 
• 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. 
• Kim JH, Han JM, Lee S, et al. (1999). "Phospholipase D1 in caveolae: regulation by protein kinase Calpha and caveolin-1.". Biochemistry 38 (12): 3763–9. doi:10.1021/bi982478. PMID 10090765. 
• Kim Y, Han JM, Park JB, et al. (1999). "Phosphorylation and activation of phospholipase D1 by protein kinase C in vivo: determination of multiple phosphorylation sites.". Biochemistry 38 (32): 10344–51. doi:10.1021/bi990579h. PMID 10441128. 
• Walker SJ, Wu WJ, Cerione RA, Brown HA (2000). "Activation of phospholipase D1 by Cdc42 requires the Rho insert region.". J. Biol. Chem. 275 (21): 15665–8. doi:10.1074/jbc.M000076200. PMID 10747870. 
• Suzuki J, Yamazaki Y, Li G, et al. (2000). "Involvement of Ras and Ral in chemotactic migration of skeletal myoblasts.". Mol. Cell. Biol. 20 (13): 4658–65. doi:10.1128/MCB.20.13.4658-4665.2000. PMC 85875. PMID 10848592. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=85875. 
• Zhang Y, Redina O, Altshuller YM, et al. (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. 
• Divecha N, Roefs M, Halstead JR, et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=314009. 
• Oishi K, Takahashi M, Mukai H, et al. (2001). "PKN regulates phospholipase D1 through direct interaction.". J. Biol. Chem. 276 (21): 18096–101. doi:10.1074/jbc.M010646200. PMID 11259428. 
• Cai S, Exton JH (2001). "Determination of interaction sites of phospholipase D1 for RhoA.". Biochem. J. 355 (Pt 3): 779–85. PMC 1221795. PMID 11311142. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1221795. 
• Lee S, Park JB, Kim JH, et al. (2001). "Actin directly interacts with phospholipase D, inhibiting its activity.". J. Biol. Chem. 276 (30): 28252–60. doi:10.1074/jbc.M008521200. PMID 11373276. 
• Hughes WE, Parker PJ (2001). "Endosomal localization of phospholipase D 1a and 1b is defined by the C-termini of the proteins, and is independent of activity.". Biochem. J. 356 (Pt 3): 727–36. doi:10.1042/0264-6021:3560727. PMC 1221899. PMID 11389680. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1221899. 
• Min DS, Ahn BH, Jo YH (2002). "Differential tyrosine phosphorylation of phospholipase D isozymes by hydrogen peroxide and the epidermal growth factor in A431 epidermoid carcinoma cells.". Mol. Cells 11 (3): 369–78. PMID 11459228.