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Gene Review

PLD1  -  phospholipase D1, phosphatidylcholine...

Homo sapiens

Synonyms: Choline phosphatase 1, PLD 1, Phosphatidylcholine-hydrolyzing phospholipase D1, Phospholipase D1, hPLD1
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Disease relevance of PLD1


Psychiatry related information on PLD1


High impact information on PLD1


Chemical compound and disease context of PLD1


Biological context of PLD1

  • We have used transposon mutagenesis to generate a library of PLD1 alleles containing random pentapeptide insertions [15].
  • Coexpression of PLD1 or PLD2 with c-Src synergistically enhances cellular proliferation compared with expression of either molecule [16].
  • Point mutations within the PLD1 PH domain inhibited enzyme activity, whereas deletion of the domain both inhibited enzyme activity and disrupted normal PLD1 localisation [17].
  • Second, a region of sequence unique to PLD1 (as compared with other PLDs) known as the "loop" region had been proposed to serve as an effector regulatory region but is shown here only to mediate inhibition of PLD1 [18].
  • Furthermore MSU crystals did not cause the tyrosine phosphorylation of PLD1 [19].

Anatomical context of PLD1

  • Using a permeabilized cell system derived from growth hormone and prolactin-secreting pituitary GH3 cells, we demonstrate that immunoaffinity-purified human PLD1 stimulated nascent secretory vesicle budding from the TGN approximately twofold [20].
  • We observed that bSMase treatment of the cells induced a larger ceramide increase in raft than in nonraft membranes and displaced both the Src kinase Lck and PLD1 out of the raft fractions [21].
  • In nuclei of dimethyl sulfoxide-treated HL-60 cells, we observed a rise in the amount of a 90-kDa PLD, distinct from PLD1 or PLD2 [22].
  • Using transiently transfected human embryonic kidney fibroblasts (HEK293), we demonstrate here that PLD1 activity, and to a lesser extent PLD2 activity, is stimulated in response to epidermal growth factor (EGF) [23].
  • These results provide evidence that two PLD1 forms are expressed in human granulocytes [24].

Associations of PLD1 with chemical compounds


Physical interactions of PLD1

  • Using in vitro binding assay, we show that ARF1 and RalA directly interact with different sites of PLD1 [30].
  • In this study, we have examined the properties of the PX domains of PLD1 and PLD2 in terms of phosphoinositide binding and PLD activity regulation [31].
  • The results obtained here indicate that PKCalpha and RhoA (GTP form) exert a synergistic action in the membrane-bound PLD activation in HL60 cells [32].
  • alpha-Synuclein interacts with phospholipase D isozymes and inhibits pervanadate-induced phospholipase D activation in human embryonic kidney-293 cells [33].
  • We report here that the mutant p53 in MDA-MB-231 cells is stabilized by the elevated PLD activity in these cells [34].

Enzymatic interactions of PLD1


Regulatory relationships of PLD1


Other interactions of PLD1


Analytical, diagnostic and therapeutic context of PLD1


  1. 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. Hammond, S.M., Jenco, J.M., Nakashima, S., Cadwallader, K., Gu, Q., Cook, S., Nozawa, Y., Prestwich, G.D., Frohman, M.A., Morris, A.J. J. Biol. Chem. (1997) [Pubmed]
  2. Expression and regulation of phospholipase D isoforms in mammalian cell lines. Gibbs, T.C., Meier, K.E. J. Cell. Physiol. (2000) [Pubmed]
  3. Selective induction of phospholipase D1 in pathogen-activated human monocytes. Locati, M., Riboldi, E., Bonecchi, R., Transidico, P., Bernasconi, S., Haribabu, B., Morris, A.J., Mantovani, A., Sozzani, S. Biochem. J. (2001) [Pubmed]
  4. Neoplastic transformation and tumorigenesis associated with overexpression of phospholipase D isozymes in cultured murine fibroblasts. Min, D.S., Kwon, T.K., Park, W.S., Chang, J.S., Park, S.K., Ahn, B.H., Ryoo, Z.Y., Lee, Y.H., Lee, Y.S., Rhie, D.J., Yoon, S.H., Hahn, S.J., Kim, M.S., Jo, Y.H. Carcinogenesis (2001) [Pubmed]
  5. Expression and regulation of phospholipase D isoenzymes in human melanoma cells and primary melanocytes. Riebeling, C., Müller, C., Geilen, C.C. Melanoma Res. (2003) [Pubmed]
  6. Phospholipase D1 is up-regulated in the mitochondrial fraction from the brains of Alzheimer's disease patients. Jin, J.K., Kim, N.H., Lee, Y.J., Kim, Y.S., Choi, E.K., Kozlowski, P.B., Park, M.H., Kim, H.S., Min, d.o. .S. Neurosci. Lett. (2006) [Pubmed]
  7. Blood phosphatidylethanol as a marker of alcohol abuse: levels in alcoholic males during withdrawal. Hansson, P., Caron, M., Johnson, G., Gustavsson, L., Alling, C. Alcohol. Clin. Exp. Res. (1997) [Pubmed]
  8. Regulation of eukaryotic phosphatidylinositol-specific phospholipase C and phospholipase D. Singer, W.D., Brown, H.A., Sternweis, P.C. Annu. Rev. Biochem. (1997) [Pubmed]
  9. Phospholipase D: enzymology, mechanisms of regulation, and function. Exton, J.H. Physiol. Rev. (1997) [Pubmed]
  10. Selective activation of nuclear phospholipase D-1 by g protein-coupled receptor agonists in vascular smooth muscle cells. Gayral, S., Déléris, P., Laulagnier, K., Laffargue, M., Salles, J.P., Perret, B., Record, M., Breton-Douillon, M. Circ. Res. (2006) [Pubmed]
  11. Effect of Rho and ADP-ribosylation factor GTPases on phospholipase D activity in intact human adenocarcinoma A549 cells. Meacci, E., Vasta, V., Moorman, J.P., Bobak, D.A., Bruni, P., Moss, J., Vaughan, M. J. Biol. Chem. (1999) [Pubmed]
  12. Differential tyrosine phosphorylation of phospholipase D isozymes by hydrogen peroxide and the epidermal growth factor in A431 epidermoid carcinoma cells. Min, D.S., Ahn, B.H., Jo, Y.H. Mol. Cells (2001) [Pubmed]
  13. Activation of phospholipase D by bradykinin and sphingosine 1-phosphate in A549 human lung adenocarcinoma cells via different GTP-binding proteins and protein kinase C delta signaling pathways. Meacci, E., Nuti, F., Catarzi, S., Vasta, V., Donati, C., Bourgoin, S., Bruni, P., Moss, J., Vaughan, M. Biochemistry (2003) [Pubmed]
  14. Phospholipase D1 is threonine-phosphorylated in human-airway epithelial cells stimulated by sphingosine-1-phosphate by a mechanism involving Src tyrosine kinase and protein kinase Cdelta. Ghelli, A., Porcelli, A.M., Facchini, A., Hrelia, S., Flamigni, F., Rugolo, M. Biochem. J. (2002) [Pubmed]
  15. Loss of receptor regulation by a phospholipase D1 mutant unresponsive to protein kinase C. Zhang, Y., Altshuller, Y.M., Hammond, S.M., Hayes, F., Morris, A.J., Frohman, M.A. EMBO J. (1999) [Pubmed]
  16. Transmodulation between phospholipase D and c-Src enhances cell proliferation. Ahn, B.H., Kim, S.Y., Kim, E.H., Choi, K.S., Kwon, T.K., Lee, Y.H., Chang, J.S., Kim, M.S., Jo, Y.H., Min, d.o. .S. Mol. Cell. Biol. (2003) [Pubmed]
  17. Phospholipase D regulation and localisation is dependent upon a phosphatidylinositol 4,5-biphosphate-specific PH domain. Hodgkin, M.N., Masson, M.R., Powner, D., Saqib, K.M., Ponting, C.P., Wakelam, M.J. Curr. Biol. (2000) [Pubmed]
  18. Structural analysis of human phospholipase D1. Sung, T.C., Zhang, Y., Morris, A.J., Frohman, M.A. J. Biol. Chem. (1999) [Pubmed]
  19. Monosodium urate-crystal-stimulated phospholipase D in human neutrophils. Marcil, J., Harbour, D., Houle, M.G., Naccache, P.H., Bourgoin, S. Biochem. J. (1999) [Pubmed]
  20. Phospholipase D stimulates release of nascent secretory vesicles from the trans-Golgi network. Chen, Y.G., Siddhanta, A., Austin, C.D., Hammond, S.M., Sung, T.C., Frohman, M.A., Morris, A.J., Shields, D. J. Cell Biol. (1997) [Pubmed]
  21. Disruption of lipid rafts stimulates phospholipase d activity in human lymphocytes: implication in the regulation of immune function. Diaz, O., Mébarek-Azzam, S., Benzaria, A., Dubois, M., Lagarde, M., Némoz, G., Prigent, A.F. J. Immunol. (2005) [Pubmed]
  22. Proliferating or differentiating stimuli act on different lipid-dependent signaling pathways in nuclei of human leukemia cells. Neri, L.M., Bortul, R., Borgatti, P., Tabellini, G., Baldini, G., Capitani, S., Martelli, A.M. Mol. Biol. Cell (2002) [Pubmed]
  23. PLD2 complexes with the EGF receptor and undergoes tyrosine phosphorylation at a single site upon agonist stimulation. Slaaby, R., Jensen, T., Hansen, H.S., Frohman, M.A., Seedorf, K. J. Biol. Chem. (1998) [Pubmed]
  24. Human phospholipase D1 can be tyrosine-phosphorylated in HL-60 granulocytes. Marcil, J., Harbour, D., Naccache, P.H., Bourgoin, S. J. Biol. Chem. (1997) [Pubmed]
  25. Activation of RBL-2H3 mast cells is dependent on tyrosine phosphorylation of phospholipase D2 by Fyn and Fgr. Choi, W.S., Hiragun, T., Lee, J.H., Kim, Y.M., Kim, H.P., Chahdi, A., Her, E., Han, J.W., Beaven, M.A. Mol. Cell. Biol. (2004) [Pubmed]
  26. Interaction of the small G protein RhoA with the C terminus of human phospholipase D1. Yamazaki, M., Zhang, Y., Watanabe, H., Yokozeki, T., Ohno, S., Kaibuchi, K., Shibata, H., Mukai, H., Ono, Y., Frohman, M.A., Kanaho, Y. J. Biol. Chem. (1999) [Pubmed]
  27. Cloning and initial characterization of a human phospholipase D2 (hPLD2). ADP-ribosylation factor regulates hPLD2. Lopez, I., Arnold, R.S., Lambeth, J.D. J. Biol. Chem. (1998) [Pubmed]
  28. Human ADP-ribosylation factor-activated phosphatidylcholine-specific phospholipase D defines a new and highly conserved gene family. Hammond, S.M., Altshuller, Y.M., Sung, T.C., Rudge, S.A., Rose, K., Engebrecht, J., Morris, A.J., Frohman, M.A. J. Biol. Chem. (1995) [Pubmed]
  29. Phospholipase D-mediated activation of IQGAP1 through Rac1 regulates hyperoxia-induced p47phox translocation and reactive oxygen species generation in lung endothelial cells. Usatyuk, P.V., Gorshkova, I.A., He, D., Zhao, Y., Kalari, S.K., Garcia, J.G., Natarajan, V. J. Biol. Chem. (2009) [Pubmed]
  30. Activation of phospholipase D1 by direct interaction with ADP-ribosylation factor 1 and RalA. 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. FEBS Lett. (1998) [Pubmed]
  31. Phosphatidylinositol (3,4,5)-trisphosphate specifically interacts with the phox homology domain of phospholipase D1 and stimulates its activity. Lee, J.S., Kim, J.H., Jang, I.H., Kim, H.S., Han, J.M., Kazlauskas, A., Yagisawa, H., Suh, P.G., Ryu, S.H. J. Cell. Sci. (2005) [Pubmed]
  32. Regulation of membrane-bound phospholipase D by protein kinase C in HL60 cells. Synergistic action of small GTP-binding protein RhoA. Ohguchi, K., Banno, Y., Nakashima, S., Nozawa, Y. J. Biol. Chem. (1996) [Pubmed]
  33. alpha-Synuclein interacts with phospholipase D isozymes and inhibits pervanadate-induced phospholipase D activation in human embryonic kidney-293 cells. Ahn, B.H., Rhim, H., Kim, S.Y., Sung, Y.M., Lee, M.Y., Choi, J.Y., Wolozin, B., Chang, J.S., Lee, Y.H., Kwon, T.K., Chung, K.C., Yoon, S.H., Hahn, S.J., Kim, M.S., Jo, Y.H., Min, d.o. .S. J. Biol. Chem. (2002) [Pubmed]
  34. Mutant p53 in MDA-MB-231 breast cancer cells is stabilized by elevated phospholipase D activity and contributes to survival signals generated by phospholipase D. Hui, L., Zheng, Y., Yan, Y., Bargonetti, J., Foster, D.A. Oncogene (2006) [Pubmed]
  35. Phospholipase D is activated and phosphorylated by casein kinase-II in human U87 astroglioma cells. Ahn, B.H., Min, G., Bae, Y.S., Bae, Y.S., Min, d.o. .S. Exp. Mol. Med. (2006) [Pubmed]
  36. A role of p44/42 mitogen-activated protein kinases in formyl-peptide receptor-mediated phospholipase D activity and oxidant production. Paruch, S., El-Benna, J., Djerdjouri, B., Marullo, S., Périanin, A. FASEB J. (2006) [Pubmed]
  37. Phospholipase D1 is phosphorylated and activated by protein kinase C in caveolin-enriched microdomains within the plasma membrane. Kim, Y., Han, J.M., Han, B.R., Lee, K.A., Kim, J.H., Lee, B.D., Jang, I.H., Suh, P.G., Ryu, S.H. J. Biol. Chem. (2000) [Pubmed]
  38. Regulation of phospholipase D by tyrosine kinases. Natarajan, V., Scribner, W.M., Vepa, S. Chem. Phys. Lipids (1996) [Pubmed]
  39. Differential role for phospholipase D1 and phospholipase D2 in 12-O-tetradecanoyl-13-phorbol acetate-stimulated MAPK activation, Cox-2 and IL-8 expression. Grab, L.T., Kearns, M.W., Morris, A.J., Daniel, L.W. Biochim. Biophys. Acta (2004) [Pubmed]
  40. Ceramide inhibition of phospholipase D and its relationship to RhoA and ARF1 translocation in GTP gamma S-stimulated polymorphonuclear leukocytes. Mansfield, P.J., Carey, S.S., Hinkovska-Galcheva, V., Shayman, J.A., Boxer, L.A. Blood (2004) [Pubmed]
  41. Regulation of phospholipase D by low molecular weight GTP-binding proteins. Kanaho, Y., Yokozeki, T., Kuribara, H. Journal of lipid mediators and cell signalling. (1996) [Pubmed]
  42. ADP-ribosylation factor, a small GTP-dependent regulatory protein, stimulates phospholipase D activity. Brown, H.A., Gutowski, S., Moomaw, C.R., Slaughter, C., Sternweis, P.C. Cell (1993) [Pubmed]
  43. Functional coupling of FcgammaRI to nicotinamide adenine dinucleotide phosphate (reduced form) oxidative burst and immune complex trafficking requires the activation of phospholipase D1. Melendez, A.J., Bruetschy, L., Floto, R.A., Harnett, M.M., Allen, J.M. Blood (2001) [Pubmed]
  44. Activation of phospholipase D by PKC and GTPgammaS in human neuroblastoma cells overexpressing MARCKS. Morash, S.C., Byers, D.M., Cook, H.W. Biochim. Biophys. Acta (2000) [Pubmed]
  45. Differential expression of phospholipase D isozymes in the hippocampus following kainic acid-induced seizures. Kim, S.Y., Min, d.o. .S., Choi, J.S., Choi, Y.S., Park, H.J., Sung, K.W., Kim, J., Lee, M.Y. J. Neuropathol. Exp. Neurol. (2004) [Pubmed]
  46. Cloning, differential regulation and tissue distribution of alternatively spliced isoforms of ADP-ribosylation-factor-dependent phospholipase D from rat liver. Katayama, K., Kodaki, T., Nagamachi, Y., Yamashita, S. Biochem. J. (1998) [Pubmed]
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