Phospholipase D in cell signaling: From a myriad of cell functions to cancer growth and metastasis

Journal of Biological Chemistry

Volumn 289, Issue 33, 2014, Pages 22557-22566

  Gomez Cambronero, Julian ^a  

^a WRIGHT STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

C (PROGRAMMING LANGUAGE); CELL MEMBRANES; CELL PROLIFERATION; DISEASES; ENZYME ACTIVITY; MAMMALS; PATHOLOGY;

CELLULAR FUNCTION; CELLULAR MEMBRANES; CYTOSKELETAL DYNAMICS; GUANINE NUCLEOTIDE EXCHANGE FACTORS; INTRACELLULAR PROTEINS; PHOSPHATIDIC ACIDS; PROTEIN-PROTEIN INTERACTIONS; WISKOTT-ALDRICH SYNDROME PROTEINS;

PROTEINS;

EPIDERMAL GROWTH FACTOR RECEPTOR; GROWTH FACTOR RECEPTOR BOUND PROTEIN 2; GUANINE NUCLEOTIDE EXCHANGE FACTOR; GUANOSINE TRIPHOSPHATASE; JANUS KINASE 3; PHOSPHATIDIC ACID; PHOSPHOLIPASE D; PHOSPHOLIPASE D1; PHOSPHOLIPASE D2; PROTEIN KINASE C; PROTEIN KINASE FES; PROTEIN TYROSINE KINASE; RAC2 PROTEIN; S6 KINASE; WISKOTT ALDRICH SYNDROME PROTEIN; GRB2 PROTEIN, HUMAN; RAC PROTEIN; TUMOR PROTEIN;

AUTOPHAGY; CANCER GROWTH; CARCINOGENESIS; CELL FUNCTION; CELL INVASION; CELL MIGRATION; COMPLEX FORMATION; ENZYME ACTIVITY; ENZYME ANALYSIS; HUMAN; METASTASIS; MOLECULAR DYNAMICS; MOLECULAR EVOLUTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; SHORT SURVEY; SIGNAL TRANSDUCTION; TUMOR INVASION; ANIMAL; CELL MEMBRANE; CELL MOTION; ENZYMOLOGY; GENETICS; METABOLISM; NEOPLASM; PATHOLOGY;

ANIMALS; CELL MEMBRANE; CELL MOVEMENT; GRB2 ADAPTOR PROTEIN; HUMANS; NEOPLASM METASTASIS; NEOPLASM PROTEINS; NEOPLASMS; PHOSPHATIDIC ACIDS; PHOSPHOLIPASE D; RAC GTP-BINDING PROTEINS; RIBOSOMAL PROTEIN S6 KINASES; SIGNAL TRANSDUCTION; WISKOTT-ALDRICH SYNDROME PROTEIN FAMILY;

EID: 84905976985     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.R114.574152     Document Type: Short Survey

References (99)

1. Wang, X., Xu, L., and Zheng, L. (1994) Cloning and expression of phos-phatidylcholine-hydrolyzing phospholipase D from Ricinus communis L. J. Biol. Chem. 269, 20312-20317 (Pubitemid 24260428)
2. Frohman, M. A., Sung, T. C., and Morris, A. J. (1999) Mammalian phospholipase D structure and regulation. Biochim. Biophys. Acta 1439, 175-186 (Pubitemid 29333130)
3. Hammond, S. M., Jenco, J. M., Nakashima, S., Cadwallader, K., Gu, Q., Cook, S., Nozawa, Y., Prestwich, G. D., Frohman, M. A., and Morris, A. J. (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-α. J. Biol. Chem. 272, 3860-3868
4. Powner, D. J., and Wakelam, M. J. (2002) The regulation of phospholipase D by inositol phospholipids and small GTPases. FEBS Lett. 531, 62-64 (Pubitemid 35232786)
5. Colley, W. C., Altshuller, Y. M., Sue-Ling, C. K., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Branch, K. D., Tsirka, S. E., Bollag, R. J., Bollag, W. B., and Frohman, M. A. (1997) Cloning and expression analysis of murine phospholipase D1. Biochem. J. 326, 745-753 (Pubitemid 27438048)
6. Kodaki, T., and Yamashita, S. (1997) Cloning, expression, and characterization of a novel phospholipase D complementary DNA from rat brain. J. Biol. Chem. 272, 11408-11413 (Pubitemid 27184146)
7. Hammond, S. M., Altshuller, Y. M., Sung, T. C., Rudge, S. A., Rose, K., Engebrecht, J., Morris, A. J., and Frohman, M. A. (1995) Human ADP-ribosylation factor-activated phosphatidylcholine-specific phospholipase D defines a new and highly conserved gene family. J. Biol. Chem. 270, 29640-29643 (Pubitemid 26001622)
8. Lopez, I., Arnold, R. S., and Lambeth, J. D. (1998) Cloning and initial characterization of a human phospholipase D2 (hPLD2): ADP-ribosylation factor regulates hPLD2. J. Biol. Chem. 273, 12846-12852 (Pubitemid 28246841)
9. Mahankali, M., Peng, H. J., Henkels, K. M., Dinauer, M. C., and Gomez-Cambronero, J. (2011) Phospholipase D2 (PLD2) is a guanine nucleotide exchange factor (GEF) for the GTPase Rac2. Proc. Natl. Acad. Sci. U.S.A. 108, 19617-19622
10. Jeon, H., Kwak, D., Noh, J., Lee, M. N., Lee, C. S., Suh, P. G., and Ryu, S. H. (2011) Phospholipase D2 induces stress fiber formation through mediating nucleotide exchange for RhoA. Cell. Signal. 23, 1320-1326
11. Mahankali, M., Henkels, K. M., Alter, G., and Gomez-Cambronero, J. (2012) Identification of the catalytic site of phospholipase D2 (PLD2) newly described guanine nucleotide exchange factor activity. J. Biol. Chem. 287, 41417-41431
12. Munck, A., Böhm, C., Seibel, N. M., Hashemol Hosseini, Z., and Hampe, W. (2005) Hu-K4 is a ubiquitously expressed type 2 transmembrane protein associated with the endoplasmic reticulum. FEBS J. 272, 1718-1726
13. Otani, Y., Yamaguchi, Y., Sato, Y., Furuichi, T., Ikenaka, K., Kitani, H., and Baba, H. (2011) PLD$ is involved in phagocytosis of microglia: expression and localization changes of PLD4 are correlated with activation state of microglia. PLoS One 6, e27544
14. Choi, S. Y., Huang, P., Jenkins, G. M., Chan, D. C., Schiller, J., and Frohman, M. A. (2006) A common lipid links Mfn-mediated mitochondrial fusion and SNARE-regulated exocytosis. Nat. Cell Biol. 8, 1255-1262 (Pubitemid 44660590)
15. Huang, H., and Frohman, M. A. (2009) Lipid signaling on the mitochondrial surface. Biochim. Biophys. Acta 1791, 839-844
16. Stace, C. L., and Ktistakis, N. T. (2006) Phosphatidic acid- and phosphati-dylserine-binding proteins. Biochim. Biophys. Acta 1761, 913-926
17. Itoh, T., Hasegawa, J., Tsujita, K., Kanaho, Y., and Takenawa, T. (2009) The tyrosine kinase Fer is a downstream target of the PLD-PA pathway that regulates cell migration. Sci. Signal. 2, ra52
18. Kooijman, E. E., Tieleman, D. P., Testerink, C., Munnik, T., Rijkers, D. T., Burger, K. N., and de Kruijff, B. (2007) An electrostatic/hydrogen bond switch as the basis for the specific interaction of phosphatidic acid with proteins. J. Biol. Chem. 282, 11356-11364 (Pubitemid 47100784)
19. Jang, J. H., Lee, C. S., Hwang, D., and Ryu, S. H. (2012) Understanding of the roles of phospholipase D and phosphatidic acid through their binding partners. Prog. Lipid Res. 51, 71-81
20. Mahankali, M., Henkels, K. M., and Gomez-Cambronero, J. (2013) AGEF-to-phospholipase molecular switch caused by phosphatidic acid, Rac and JAK tyrosine kinase that explains leukocyte cell migration. J. Cell Sci. 126, 1416-1428
21. Chen, J. S., and Exton, J. H. (2004) Regulation of phospholipase D2 activity by protein kinase C α. J. Biol. Chem. 279, 22076-22083
22. Oishi, K., Takahashi, M., Mukai, H., Banno, Y., Nakashima, S., Kanaho, Y., Nozawa, Y., and Ono, Y. (2001) PKN regulates phospholipase D1 through direct interaction. J. Biol. Chem. 276, 18096-18101
23. Chae, Y. C., Kim, K. L., Ha, S. H., Kim, J., Suh, P. G., and Ryu, S. H. (2010) Protein kinase Cδ-mediated phosphorylation of phospholipase D controls integrin-mediated cell spreading. Mol. Cell. Biol. 30, 5086-5098
24. Jang, I. H., Lee, S., Park, J. B., Kim, J. H., Lee, C. S., Hur, E. M., Kim, I. S., Kim, K. T., Yagisawa, H., Suh, P. G., and Ryu, S. H. (2003) The direct interaction of phospholipase C-γ1 with phospholipase D2 is important for epidermal growth factor signaling. J. Biol. Chem. 278, 18184-18190 (Pubitemid 36799434)
25. Lee, H. Y., Jung, H., Jang, I. H., Suh, P. G., and Ryu, S. H. (2008) Cdk5 phosphorylates PLD2 to mediate EGF-dependent insulin secretion. Cell. Signal. 20, 1787-1794
26. Di Fulvio, M., Lehman, N., Lin, X., Lopez, I., and Gomez-Cambronero, J. (2006) The elucidation of novel SH2 binding sites on PLD2. Oncogene 25, 3032-3040 (Pubitemid 43780467)
27. Choi, W. S., Hiragun, T., Lee, J. H., Kim, Y. M., Kim, H. P., Chahdi, A., Her, E., Han, J. W., and Beaven, M. A. (2004) Activation of RBL-2H3 mast cells is dependent on tyrosine phosphorylation of phospholipase D2 by Fyn and Fgr. Mol. Cell. Biol. 24, 6980-6992 (Pubitemid 39014426)
28. Henkels, K. M., Peng, H. J., Frondorf, K., and Gomez-Cambronero, J. (2010) A comprehensive model that explains the regulation of phospholipase D2 activity by phosphorylation-dephosphorylation. Mol. Cell. Biol. 30, 2251-2263
29. Xu, L., Frankel, P., Jackson, D., Rotunda, T., Boshans, R. L., D'Souza-Schorey, C., and Foster, D. A. (2003) Elevated phospholipase D activity in H-Ras- but not K-Ras-transformed cells by the synergistic action of RalA and ARF6. Mol. Cell. Biol. 23, 645-654 (Pubitemid 36050557)
30. Ye, Q., Kantonen, S., Henkels, K. M., and Gomez-Cambronero, J. (2013) A new signaling pathway (JAK-Fes-phospholipase D) that is enhanced in highly proliferative breast cancer cells. J. Biol Chem. 288, 9881-9891
31. Divecha, N., Roefs, M., Halstead, J. R., D'Andrea, S., Fernandez-Borga, M., Oomen, L., Saqib, K. M., Wakelam, M. J., and D'Santos, C. (2000) Interaction of the type Iα PIPkinase with phospholipase D: a role for the local generation of phosphatidylinositol 4, 5-bisphosphate in the regulation of PLD2 activity. EMBO J. 19, 5440-5449
32. Peng, H. J., Henkels, K. M., Mahankali, M., Dinauer, M. C., and Gomez-Cambronero, J. (2011) Evidence for two CRIB domains in phospholipase D2 (PLD2) that the enzyme uses to specifically bind to the small GTPase Rac2. J. Biol. Chem. 286, 16308-16320
33. Kim, J. H., Lee, S. D., Han, J. M., Lee, T. G., Kim, Y., Park, J. B., Lambeth, J. D., Suh, P. G., and Ryu, S. H. (1998) Activation of phospholipase D1 by direct interaction with ADP-ribosylation factor 1 and RalA. FEBS Lett. 430, 231-235 (Pubitemid 28337919)
34. Bae, C. D., Min, D. S., Fleming, I. N., and Exton, J. H. (1998) Determination of interaction sites on the small G protein RhoA for phospholipase D. J. Biol. Chem. 273, 11596-11604 (Pubitemid 28272058)
35. Yamazaki, M., Zhang, Y., Watanabe, H., Yokozeki, T., Ohno, S., Kaibuchi, K., Shibata, H., Mukai, H., Ono, Y., Frohman, M. A., and Kanaho, Y. (1999) Interaction of the small G protein RhoA with the C terminus of human phospholipase D1. J. Biol. Chem. 274, 6035-6038 (Pubitemid 29111004)
36. Peng, H. J., Henkels, K. M., Mahankali, M., Marchal, C., Bubulya, P., Dinauer, M. C., Gomez-Cambronero, J. (2011) The dual effect of Rac2 on phospholipase D2 regulation that explains both the onset and termination of chemotaxis. Mol. Cell. Biol. 31, 2227-2240
37. Speranza, F. J., Mahankali, M., and Gomez-Cambronero, J. (2013) Macrophage migration arrest due to a winning balance of Rac2/Sp1 repression over β-catenin-induced PLD expression. J. Leukoc. Biol. 94, 953-962
38. Pathre, P., Shome, K., Blumental-Perry, A., Bielli, A., Haney, C. J., Alber, S., Watkins, S. C., Romero, G., and Aridor, M. (2003) Activation of phospholipase D by the small GTPase Sar1p is required to support COPII assembly and ER export. EMBO J. 22, 4059-4069 (Pubitemid 37021735)
39. Speranza, F. J., Mahankali, M., and Gomez-Cambronero, J. (2013) Macrophage migration arrest due to a winning balance of Rac2/Sp1 repression over β-catenin-induced PLD expression. J. Leukoc. Biol. 94, 953-962
40. Lee, C. S., Kim, I. S., Park, J. B., Lee, M. N., Lee, H. Y., Suh, P. G., and Ryu, S. H. (2006) The phox homology domain of phospholipase D activates dynamin GTPase activity and accelerates EGFR endocytosis. Nat. Cell Biol. 8, 477-484
41. Henkels, K. M., Mahankali, M., and Gomez-Cambronero, J. (2013) Increased cell growth due to a new lipase-GEF (Phospholipase D2) fastly acting on Ras. Cell. Signal. 25, 198-205
42. Eckert, L. B., Repasky, G. A., Ulkü, A. S., McFall, A., Zhou, H., Sartor, C. I., and Der, C. J. (2004) Involvement of Ras activation in human breast cancer cell signaling, invasion, and anoikis. Cancer Res. 64, 4585-4592 (Pubitemid 38856932)
43. Lehman, N., Di Fulvio, M., McCray, N., Campos, I., Tabatabaian, F., and Gomez-Cambronero, J. (2006) Phagocyte cell migration is mediated by phospholipases PLD1 and PLD2. Blood 108, 3564-3572
44. Santy, L. C., and Casanova, J. E. (2001) Activation of ARF6 by ARNO stimulates epithelial cell migration through downstream activation of both Rac1 and phospholipase D. J. Cell Biol. 154, 599-610 (Pubitemid 34286164)
45. Zouwail, S., Pettitt, T. R., Dove, S. K., Chibalina, M. V., Powner, D. J., Haynes, L., Wakelam, M. J., and Insall, R. H. (2005) Phospholipase D activity is essential for actin localization and actin-based motility in Dictyostelium. Biochem. J. 389, 207-214 (Pubitemid 40978024)
46. Powner, D. J., Payne, R. M., Pettitt, T. R., Giudici, M. L., Irvine, R. F., and Wakelam, M. J. (2005) Phospholipase D2 stimulates integrin-mediated adhesion via phosphatidylinositol 4-phosphate 5-kinase Iγb. J. Cell Sci. 118, 2975-2986 (Pubitemid 41136374)
47. Corrotte, M., Chasserot-Golaz, S., Huang, P., Du, G., Ktistakis, N. T., Frohman, M. A., Vitale, N., Bader, M. F., and Grant, N. J. (2006) Dynamics and function of phospholipase D and phosphatidic acid during phagocytosis. Traffic 7, 365-377 (Pubitemid 43323962)
48. Ali, W. H., Chen, Q., Delgiorno, K. E., Su, W., Hall, J. C., Hongu, T., Tian, H., Kanaho, Y., Di Paolo, G., Crawford, H. C., and Frohman, M. A. (2013) Deficiencies of the lipid-signaling enzymes phospholipase D1 and D2 alter cytoskeletal organization, macrophage phagocytosis, and cytokine-stimulated neutrophil recruitment. PLoS One 8, e55325
49. Frondorf, K., Henkels, K. M., Frohman, M. A., and Gomez-Cambronero, J. (2010) Phosphatidic acid (PA) is a leukocyte chemoattractant that acts through S6 kinase signaling. J. Biol. Chem. 285, 15837-15847
50. Su, W., Yeku, O., Olepu, S., Genna, A., Park, J. S., Ren, H., Du, G., Gelb, M. H., Morris, A. J., and Frohman, M. A. (2009) 5-Fluoro-2-indolyl deschlorohalopemide (FIPI), a phospholipase D pharmacological inhibitor that alters cell spreading and inhibits chemotaxis. Mol. Pharmacol. 75, 437-446
51. Nishikimi, A., Fukuhara, H., Su, W., Hongu, T., Takasuga, S., Mihara, H., Cao, Q., Sanematsu, F., Kanai, M., Hasegawa, H., Tanaka, Y., Shibasaki, M., Kanaho, Y., Sasaki, T., Frohman, M. A., and Fukui, Y. (2009) Sequential regulation of DOCK2 dynamics by two phospholipids during neutrophil chemotaxis. Science 324, 384-387
52. Gomez-Cambronero, J. (2012) Structure analysis between the SWAP-70 RHO-GEF and the newly described PLD2-GEF. Small GTPases 3, 202-208
53. Kam, Y., and Exton, J. H. (2001) Phospholipase D activity is required for actin stress fiber formation in fibroblasts. Mol. Cell. Biol. 21, 4055-4066 (Pubitemid 32476466)
54. Di Fulvio, M., Frondorf, K., Henkels, K. M., Lehman, N., and Gomez-Cambronero, J. (2007) The Grb2/PLD2 interaction is essential for lipase activity, intracellular localization and signaling in response to EGF. J. Mol. Biol. 367, 814-824 (Pubitemid 46330378)
55. Kantonen, S., Hatton, N., Mahankali, M., Henkels, K. M., Park, H., Cox, D., and Gomez-Cambronero, J. (2011) A novel phospholipase D2-Grb2-WASp heterotrimer regulates leukocyte phagocytosis in a two-step mechanism. Mol. Cell. Biol. 31, 4524-4537
56. Mahankali, M., Peng, H. J., Cox, D., and Gomez-Cambronero, J. (2011) The mechanism of cell membrane ruffling relies on a phospholipase D2 (PLD2), Grb2 and Rac2 association. Cell. Signal. 23, 1291-1298
57. Knapek, K., Frondorf, K., Post, J., Short, S., Cox, D., and Gomez-Cambronero, J. (2010) The molecular basis of phospholipase D2-induced chemotaxis: elucidation of differential pathways in macrophages and fibroblasts. Mol. Cell. Biol. 30, 4492-4506
58. Delon, C., Manifava, M., Wood, E., Thompson, D., Krugmann, S., Pyne, S., and Ktistakis, N. T. (2004) Sphingosine kinase 1 is an intracellular effector of phosphatidic acid. J. Biol. Chem. 279, 44763-44774 (Pubitemid 39430887)
59. Pchejetski, D., Golzio, M., Bonhoure, E., Calvet, C., Doumerc, N., Garcia, V., Mazerolles, C., Rischmann, P., Teissié, J., Malavaud, B., and Cuvillier, O. (2005) Sphingosine kinase-1 as a chemotherapy sensor in prostate adenocarcinoma cell and mouse models. Cancer Res. 65, 11667-11675 (Pubitemid 41821727)
60. Nava, V. E., Hobson, J. P., Murthy, S., Milstien, S., and Spiegel, S. (2002) Sphingosine kinase type 1 promotes estrogen-dependent tumorigenesis of breast cancer MCF-7 cells. Exp. Cell Res. 281, 115-127 (Pubitemid 35373788)
61. Pyne, N. J., and Pyne, S. (2010) Sphingosine 1-phosphate and cancer. Nat. Rev. Cancer 10, 489-503
62. Brindley, D. N., and Waggoner, D. W. (1998) Mammalian lipid phosphate phosphohydrolases. J. Biol. Chem. 273, 24281-24284 (Pubitemid 28454910)
63. Jasinska, R., Zhang, Q. X., Pilquil, C., Singh, I., Xu, J., Dewald, J., Dillon, D. A., Berthiaume, L. G., Carman, G. M., Waggoner, D. W., and Brindley, D. N. (1999) Lipid phosphate phosphohydrolase-1 degrades exogenous glycerolipid and sphingolipid phosphate esters. Biochem. J. 340, 677-686 (Pubitemid 29312864)
64. Brindley, D. N., and Pilquil, C. (2009) Lipid phosphate phosphatases and signaling. J. Lipid Res. 50, (suppl.) S225-S230
65. Zheng, Y., Rodrik, V., Toschi, A., Shi, M., Hui, L., Shen, Y., and Foster, D. A. (2006) Phospholipase D couples survival and migration signals in stress response of human cancer cells. J. Biol. Chem. 281, 15862-15868 (Pubitemid 43848477)
66. Yamada, Y., Hamajima, N., Kato, T., Iwata, H., Yamamura, Y., Shinoda, M., Suyama, M., Mitsudomi, T., Tajima, K., Kusakabe, S., Yoshida, H., Banno, Y., Akao, Y., Tanaka, M., and Nozawa, Y. (2003) Association of a polymorphism of the phospholipase D2 gene with the prevalence of colorectal cancer. J. Mol. Med. 81, 126-131 (Pubitemid 36313238)
67. Saito, M., Iwadate, M., Higashimoto, M., Ono, K., Takebayashi, Y., and Takenoshita, S. (2007) Expression of phospholipase D2 in human colorectal carcinoma. Oncol. Rep. 18, 1329-1334
68. Toschi, A., Edelstein, J., Rockwell, P., Ohh, M., and Foster, D. A. (2008) HIFα expression in VHL-deficient renal cancer cells is dependent on phospholipase D. Oncogene 27, 2746-2753 (Pubitemid 351581463)
69. Luquain, C., Singh, A., Wang, L., Natarajan, V., and Morris, A. J. (2003) Role of phospholipase D in agonist-stimulated lysophosphatidic acid synthesis by ovarian cancer cells. J. Lipid Res. 44, 1963-1975 (Pubitemid 37356669)
70. Oh, K. J., Lee, S. C., Choi, H. J., Oh, D. Y., Kim, S. C., Min do, S., Kim, J. M., Lee, K. S., and Han, J. S. (2007) Role of phospholipase D2 in anti-apoptotic signaling through increased expressions of Bcl-2 and Bcl-xL. J. Cell. Biochem. 101, 1409-1422
71. Shi, M., Zheng, Y., Garcia, A., Xu, L., and Foster, D. A. (2007) Phospholipase D provides a survival signal in human cancer cells with activated H-Ras or K-Ras. Cancer Lett. 258, 268-275 (Pubitemid 350101020)
72. Nozawa, S., Ohno, T., Banno, Y., Dohjima, T., Wakahara, K., Fan, D. G., and Shimizu, K. (2005) Inhibition of platelet-derived growth factor-induced cell growth signaling by a short interfering RNA for EWS-Fli1 via down-regulation of phospholipase D2 in Ewing sarcoma cells. J. Biol. Chem. 280, 27544-27551 (Pubitemid 41076865)
73. Kim, Y. R., Byun, H. S., Won, M., Park, K. A., Kim, J. M., Choi, B. L., Lee, H., Hong, J. H., Park, J., Seok, J. H., Kim, D. W., Shong, M., Park, S. K., and Hur, G. M. (2008) Modulatory role of phospholipase D in the activation of signal transducer and activator of transcription (STAT)-3 by thyroid oncogenic kinase RET/PTC. BMC Cancer 8, 144
74. Di Fulvio, M., Frondorf, K., and Gomez-Cambronero, J. (2008) Mutation of Y179 on phospholipase D2 (PLD2) upregulates DNA synthesis in a PI3K- and Akt-dependent manner. Cell. Signal. 20, 176-185 (Pubitemid 350138379)
75. Knoepp, S. M., Chahal, M. S., Xie, Y., Zhang, Z., Brauner, D. J., Hallman, M. A., Robinson, S. A., Han, S., Imai, M., Tomlinson, S., and Meier, K. E. (2008) Effects of active and inactive phospholipase D2 on signal transduction, adhesion, migration, invasion, and metastasis in EL4 lymphoma cells. Mol. Pharmacol. 74, 574-584
76. Park, M. H., Ahn, B. H., Hong, Y. K., and Min do, S. (2009) Overexpression of phospholipase D enhances matrix metalloproteinase-2 expression and glioma cell invasion via protein kinase C and protein kinase A/NF-κB/Sp1-mediated signaling pathways. Carcinogenesis 30, 356-365
77. Henkels, K. M., Farkaly, T., Mahankali, M., Segall, J. E., and Gomez-Cambronero, J. (2011) Cell invasion of highly metastatic MTLn3 cancer cells is dependent on phospholipase D2 (PLD2) and Janus kinase 3 (JAK3). J. Mol. Biol. 408, 850-862
78. Ye, Q., Kantonen, S., and Gomez-Cambronero, J. (2013) Serum deprivation confers the MDA-MB-231 breast cancer line with an EGFR/JAK3/PLD2 system that maximizes cancer cell invasion. J. Mol. Biol. 425, 755-766
79. Lavieri, R. R., Scott, S. A., Selvy, P. E., Kim, K., Jadhav, S., Morrison, R. D., Daniels, J. S., Brown, H. A., and Lindsley, C. W. (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, 6706-6719
80. Henkels, K. M., Boivin, G. P., Dudley, E. S., Berberich, S. J., and Gomez-Cambronero, J. (2013) Phospholipase D (PLD) drives cell invasion, tumor growth and metastasis in a human breast cancer xenograph model. Oncogene 32, 5551-5562
81. Chen, Q., Hongu, T., Sato, T., Zhang, Y., Ali, W., Cavallo, J. A., van der Velden, A., Tian, H., Di Paolo, G., Nieswandt, B., Kanaho, Y., and Frohman, M. A. (2012) Key roles for the lipid signaling enzyme phospholipase D1 in the tumor microenvironment during tumor angiogenesis and metastasis. Sci. Signal. 5, ra79
82. O'Reilly, M. C., Scott, S. A., Brown, K. A., Oguin, T. H., 3rd, Thomas, P. G., Daniels, J. S., Morrison, R., Brown, H. A., and Lindsley, C. W. (2013) Development of dual PLD1/2 and PLD2 selective inhibitors from a common 1,3,8-triazaspiro[4.5]decane core: discovery of Ml298 and Ml299 that decrease invasive migration in U87-MG glioblastoma cells. J. Med. Chem. 56, 2695-2699
83. Kang, D. W., Lee, S. H., Yoon, J. W., Park, W. S., Choi, K. Y., and Min do, S. (2010) Phospholipase D1 drives a positive feedback loop to reinforce the Wnt/β-catenin/TCF signaling axis. Cancer Res. 70, 4233-4242
84. Kang, D. W., and Min do, S. (2010) Positive feedback regulation between phospholipase D and Wnt signaling promotes Wnt-driven anchorage-independent growth of colorectal cancer cells. PLoS One 5, e12109
85. Kang, D. W., Min, G., Park do, Y., Hong, K. W., and Min do, S. (2010) Rebamipide-induced downregulation of phospholipase D inhibits inflammation and proliferation in gastric cancer cells. Exp. Mol. Med. 42, 555-564
86. Hsu, Y. L., Hung, J. Y., Ko, Y. C., Hung, C. H., Huang, M. S., and Kuo, P. L. (2010) Phospholipase D signaling pathway is involved in lung cancerderived IL-8 increased osteoclastogenesis. Carcinogenesis 31, 587-596
87. Su, W., Chen, Q., and Frohman, M. A. (2009) Targeting phospholipase D with small-molecule inhibitors as a potential therapeutic approach for cancer metastasis. Future Oncol. 5, 1477-1486
88. Kang, D. W., Lee, J. Y., Oh, D. H., Park, S. Y., Woo, T. M., Kim, M. K., Park, M. H., Jang, Y. H., and Min do, S. (2009) Triptolide-induced suppression of phospholipase D expression inhibits proliferation of MDA-MB-231 breast cancer cells. Exp. Mol. Med. 41, 678-685
89. Kulkarni, A., Quang, P., Curry, V., Keyes, R., Zhou, W., Cho, H., Baffoe, J., Török, B., and Stieglitz, K. (2014) 1,3-Disubstituted-4- aminopyrazolo [3, 4-d] pyrimidines, a new class of potent inhibitors for Phospholipase D. Chem. Biol. Drug Des. 10.1111/cbdd.12319
90. Kang, D. W., Hwang, W. C., Park, M. H., Ko, G. H., Ha, W. S., Kim, K. S., Lee, Y. C., Choi, K. Y., and Min, D. S. (2013) Rebamipide abolishes Helicobacter pylori CagA-induced phospholipase D1 expression via inhibition of NFκB and suppresses invasion of gastric cancer cells. Oncogene 32, 3531-3542
91. Zhang, F., Wang, Z., Lu, M., Yonekubo, Y., Liang, X., Zhang, Y., Wu, P., Zhou, Y., Grinstein, S., Hancock, J. F., and Du, G. (2014) Temporal production of the signaling lipid phosphatidic acid by phospholipase D2 determines the output of extracellular signal-regulated kinase signaling in cancer cells. Mol. Cell. Biol. 34, 84-95
92. Cipriano, R., Bryson, B. L., Miskimen, K. L., Bartel, C. A., Hernandez-Sanchez, W., Bruntz, R. C., Scott, S. A., Lindsley, C. W., Brown, H. A., and Jackson, M. W. (2014) Hyperactivation of EGFR and downstream effector phospholipase D1 by oncogenic FAM83B. Oncogene 33, 3298-3306
93. Cheol Son, J., Woo Kang, D., Mo Yang, K., Choi, K. Y., Gen Son, T., and Min Do, S. (2013) Phospholipase D inhibitor enhances radiosensitivity of breast cancer cells. Exp. Mol. Med. 45, e38
94. Schwartz, N., Chaudhri, R. A., Hadadi, A., Schwartz, Z., and Boyan, B. D. (2014) 17β-Estradiol promotes aggressive laryngeal cancer through membrane-associated estrogen receptor-α 36. Horm. Cancer 5, 22-32
95. Pye, D. S., Rubio, I., Pusch, R., Lin, K., Pettitt, A. R., and Till, K. J. (2013) Chemokine unresponsiveness of chronic lymphocytic leukemia cells results from impaired endosomal recycling of Rap1 and is associated with a distinctive type of immunological anergy. J. Immunol. 191, 1496-1504
96. Marguerite, V., Gkikopoulou, E., Alberto, J. M., Guéant, J. L., and Merten, M. (2013) Phospholipase D activation mediates cobalamin-induced downregulation of Multidrug Resistance-1 gene and increase in sensitivity to vinblastine in HepG2 cells. Int. J. Biochem. Cell Biol. 45, 213-220
97. Jang, Y. H., Choi, K. Y., and Min, D. S. (2014) Phospholipase D-mediated autophagic regulation is a potential target for cancer therapy. Cell Death Differ. 21, 533-546
98. Bruntz, R. C., Taylor, H. E., Lindsley, C. W., and Brown, H. A. (2014) Phospholipase D2 mediates survival signaling through direct regulation of Akt in glioblastoma cells. J. Biol. Chem. 289, 600-616
99. Selvy, P. E., Lavieri, R. R., Lindsley, C. W., and Brown, H. A. (2011) Phospholipase D: enzymology, functionality, and chemical modulation. Chem. Rev. 111, 6064-6119