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Gene Review

Pld1  -  phospholipase D1

Mus musculus

Synonyms: AA536939, C85393, Choline phosphatase 1, PLD 1, Phosphatidylcholine-hydrolyzing phospholipase D1, ...
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Disease relevance of Pld1

  • Treatment of B16 mouse melanoma cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in the activation of PLD and a decrease in melanin content [1].
  • Here, we investigated the expression of PLD during differentiation of pluripotent embryonal carcinoma cells (P19) into astrocytes and neurons [2].
  • Involvement of phospholipase D1 in melanogenesis of mouse B16 melanoma cells [3].
  • We found that Streptomyces sp. PLD was much less potent at inhibiting proliferation than S. chromofuscus PLD, with a half-maximal inhibitory concentration of 0.05 versus less than 0.001 IU per ml for S. chromofuscus PLD [4].
  • A20 murine lymphoma cells undergoing Fas-mediated apoptosis showed increase in the activity of phospholipase D (PLD), which is involved in proliferative or mitogenic cellular responses [5].

Psychiatry related information on Pld1

  • The subcellular localization of PLD1 is altered, and PLD enzymatic activity is reduced in cells expressing familial Alzheimer's disease (FAD) PS1 mutations compared with PS1wt cells [6].

High impact information on Pld1

  • An early response to the tyrosine kinase activity of v-Src is an increase in phospholipase D (PLD) activity, which leads to the generation of biologically active lipid second messengers, including phosphatidic acid, lysophosphatidic acid and diacylglycerol [7].
  • Thus RalA is involved in the tyrosine kinase activation of PLD through its unique N terminus, and that PLD is a downstream target of a Ras/Ral GTPase cascade [7].
  • However, there was no PLD activation nor chlamydial killing in ATP-treated P2X(7)R-deficient macrophages [8].
  • P2X(7)R stimulation also resulted in macrophage death, but fusion with lysosomes preceded macrophage death and PLD inhibition did not prevent macrophage death [8].
  • Overexpression of PLD1 in PS1wt cells promotes generation of betaAPP-containing vesicles from the trans-Golgi network [6].

Chemical compound and disease context of Pld1


Biological context of Pld1


Anatomical context of Pld1


Associations of Pld1 with chemical compounds


Physical interactions of Pld1

  • Recombinantly expressed PLD2 has high basal activity and is insensitive to GTP-binding protein activators of PLD1 [Colley, W. C., et al. (1997) Curr. Biol. 7, 191-201] [19].
  • Investigating possible mitogenic signaling pathways we show for the first time that prolactin is coupled to a sustained phospholipase D (PLD) activation, with an efficacy similar to the phorbol ester and astrocytic mitogen 12-tetradecanoylphorbol-13-acetate (TPA) [20].

Regulatory relationships of Pld1


Other interactions of Pld1


Analytical, diagnostic and therapeutic context of Pld1


  1. Down-regulation of melanogenesis by phospholipase D2 through ubiquitin proteasome-mediated degradation of tyrosinase. Kageyama, A., Oka, M., Okada, T., Nakamura, S., Ueyama, T., Saito, N., Hearing, V.J., Ichihashi, M., Nishigori, C. J. Biol. Chem. (2004) [Pubmed]
  2. Retinoic acid-induced differentiation into astrocytes and glutamatergic neurons is associated with expression of functional and activable phospholipase D. Rujano, M.A., Pina, P., Servitja, J.M., Ahumada, A.M., Picatoste, F., Farrés, J., Sabrià, J. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  3. Involvement of phospholipase D1 in melanogenesis of mouse B16 melanoma cells. Ohguchi, K., Banno, Y., Akao, Y., Nozawa, Y. J. Biol. Chem. (2004) [Pubmed]
  4. A potential role for ceramide in the regulation of mouse epidermal keratinocyte proliferation and differentiation. Jung, E.M., Griner, R.D., Mann-Blakeney, R., Bollag, W.B. J. Invest. Dermatol. (1998) [Pubmed]
  5. Differential effects of Fas cross-linking on phospholipase D activation and related lipid metabolism in Fas-resistant A20 cells. Lim, S.Y., Lee, S.C., Shin, I., Han, J.S. Exp. Mol. Med. (2002) [Pubmed]
  6. Phospholipase D1 corrects impaired betaAPP trafficking and neurite outgrowth in familial Alzheimer's disease-linked presenilin-1 mutant neurons. Cai, D., Zhong, M., Wang, R., Netzer, W.J., Shields, D., Zheng, H., Sisodia, S.S., Foster, D.A., Gorelick, F.S., Xu, H., Greengard, P. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  7. Involvement of Ral GTPase in v-Src-induced phospholipase D activation. Jiang, H., Luo, J.Q., Urano, T., Frankel, P., Lu, Z., Foster, D.A., Feig, L.A. Nature (1995) [Pubmed]
  8. Inhibition of chlamydial infectious activity due to P2X7R-dependent phospholipase D activation. Coutinho-Silva, R., Stahl, L., Raymond, M.N., Jungas, T., Verbeke, P., Burnstock, G., Darville, T., Ojcius, D.M. Immunity (2003) [Pubmed]
  9. Effect of prostaglandin E2 on phospholipase D activity in osteoblast-like MC3T3-E1 cells. Oiso, Y., Suzuki, A., Kozawa, O. J. Bone Miner. Res. (1995) [Pubmed]
  10. Stimulation of phospholipase D activity by oxidized LDL in mouse peritoneal macrophages. Gómez-Muñoz, A., Martens, J.S., Steinbrecher, U.P. Arterioscler. Thromb. Vasc. Biol. (2000) [Pubmed]
  11. Increased expression of phospholipase D1 in the brains of scrapie-infected mice. Jin, J.K., Kim, N.H., Min, d.o. .S., Kim, J.I., Choi, J.K., Jeong, B.H., Choi, S.I., Choi, E.K., Carp, R.I., Kim, Y.S. J. Neurochem. (2005) [Pubmed]
  12. Lysophosphatidylcholine stimulates phospholipase D activity in mouse peritoneal macrophages. Gómez-Muñoz, A., O'Brien, L., Hundal, R., Steinbrecher, U.P. J. Lipid Res. (1999) [Pubmed]
  13. Genomic analysis of murine phospholipase D1 and comparison to phospholipase D2 reveals an unusual difference in gene size. Redina, O.E., Frohman, M.A. Gene (1998) [Pubmed]
  14. Participation of phospholipase D and alpha/beta-protein kinase C in growth factor-induced signalling in C3H10T1/2 fibroblasts. Thorsen, V.A., Vorland, M., Bjørndal, B., Bruland, O., Holmsen, H., Lillehaug, J.R. Biochim. Biophys. Acta (2003) [Pubmed]
  15. Increased expression of two phospholipase D isoforms during experimentally induced hippocampal mossy fiber outgrowth. Zhang, Y., Huang, P., Du, G., Kanaho, Y., Frohman, M.A., Tsirka, S.E. Glia (2004) [Pubmed]
  16. 1,25-dihydroxyvitamin D3 induces phospholipase D-1 expression in primary mouse epidermal keratinocytes. Griner, R.D., Qin, F., Jung, E., Sue-Ling, C.K., Crawford, K.B., Mann-Blakeney, R., Bollag, R.J., Bollag, W.B. J. Biol. Chem. (1999) [Pubmed]
  17. Phospholipase D2 functions as a downstream signaling molecule of MAP kinase pathway in L1-stimulated neurite outgrowth of cerebellar granule neurons. Watanabe, H., Yamazaki, M., Miyazaki, H., Arikawa, C., Itoh, K., Sasaki, T., Maehama, T., Frohman, M.A., Kanaho, Y. J. Neurochem. (2004) [Pubmed]
  18. Enhancement of phospholipase D activity by overexpression of amyloid precursor protein in P19 mouse embryonic carcinoma cells. Lee, M.J., Oh, J.Y., Park, H.T., Uhlinger, D.J., Kwak, J.Y. Neurosci. Lett. (2001) [Pubmed]
  19. Regulation of phospholipase D2: selective inhibition of mammalian phospholipase D isoenzymes by alpha- and beta-synucleins. Jenco, J.M., Rawlingson, A., Daniels, B., Morris, A.J. Biochemistry (1998) [Pubmed]
  20. Prolactin concurrently activates src-PLD and JAK/Stat signaling pathways to induce proliferation while promoting differentiation in embryonic astrocytes. Mangoura, D., Pelletiere, C., Leung, S., Sakellaridis, N., Wang, D.X. Int. J. Dev. Neurosci. (2000) [Pubmed]
  21. Arf1-dependent PLD1 is localized to oleic acid-induced lipid droplets in NIH3T3 cells. Nakamura, N., Banno, Y., Tamiya-Koizumi, K. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  22. Activation of phospholipase D-2 by P2X(7) agonists in rat submandibular gland acini. Pérez-Andrés, E., Fernández-Rodriguez, M., González, M., Zubiaga, A., Vallejo, A., García, I., Matute, C., Pochet, S., Dehaye, J.P., Trueba, M., Marino, A., Gómez-Muñoz, A. J. Lipid Res. (2002) [Pubmed]
  23. Phospholipase d signaling and extracellular signal-regulated kinase-1 and -2 phosphorylation (activation) are required for maximal phorbol ester-induced transglutaminase activity, a marker of keratinocyte differentiation. Bollag, W.B., Zhong, X., Dodd, M.E., Hardy, D.M., Zheng, X., Allred, W.T. J. Pharmacol. Exp. Ther. (2005) [Pubmed]
  24. Dissociation of the pore-forming and phospholipase D activities stimulated via P2z purinergic receptors in BAC1.2F5 macrophages. Product inhibition of phospholipase D enzyme activity. el-Moatassim, C., Dubyak, G.R. J. Biol. Chem. (1993) [Pubmed]
  25. Insulin-stimulated plasma membrane fusion of Glut4 glucose transporter-containing vesicles is regulated by phospholipase D1. Huang, P., Altshuller, Y.M., Hou, J.C., Pessin, J.E., Frohman, M.A. Mol. Biol. Cell (2005) [Pubmed]
  26. Dexamethasone enhances phospholipase D activity in M-1 cells. Kim, W.J., Lee, M.J., Park, M.A., Jung, J.S., Uhlinger, D.J., Kwak, J.Y. Exp. Mol. Med. (2000) [Pubmed]
  27. 3T3-L1 adipocytes express two isoforms of phospholipase D in distinct subcellular compartments. Millar, C.A., Jess, T.J., Saqib, K.M., Wakelam, M.J., Gould, G.W. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  28. A role for phospholipase D in GLUT4 glucose transporter translocation. Emoto, M., Klarlund, J.K., Waters, S.B., Hu, V., Buxton, J.M., Chawla, A., Czech, M.P. J. Biol. Chem. (2000) [Pubmed]
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