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Phospholipase D and the Mitogen Phosphatidic Acid in Human Disease: Inhibitors of PLD at the Crossroads of Phospholipid Biology and Cancer.

Gomez-Cambronero J, Shah KN.

Handb Exp Pharmacol. 2019 Sep 21. doi: 10.1007/164_2019_216. [Epub ahead of print]


The Epidermal Growth Factor Receptor Ligand Amphiregulin Protects From Cholestatic Liver Injury and Regulates Bile Acids Synthesis.

Santamaría E, Rodríguez-Ortigosa CM, Uriarte I, Latasa MU, Urtasun R, Alvarez-Sola G, Bárcena-Varela M, Colyn L, Arcelus S, Jiménez M, Deutschmann K, Peleteiro-Vigil A, Gómez-Cambronero J, Milkiewicz M, Milkiewicz P, Sangro B, Keitel V, Monte MJ, Marin JJG, Fernández-Barrena MG, Ávila MA, Berasain C.

Hepatology. 2019 Apr;69(4):1632-1647. doi: 10.1002/hep.30348. Epub 2019 Mar 4.


Tumor cell-secreted PLD increases tumor stemness by senescence-mediated communication with microenvironment.

Muñoz-Galván S, Lucena-Cacace A, Perez M, Otero-Albiol D, Gomez-Cambronero J, Carnero A.

Oncogene. 2019 Feb;38(8):1309-1323. doi: 10.1038/s41388-018-0527-2. Epub 2018 Oct 10.


Targeting Phospholipase D Genetically and Pharmacologically for Studying Leukocyte Function.

Gomez-Cambronero J, Ganesan R.

Methods Mol Biol. 2018;1835:297-314. doi: 10.1007/978-1-4939-8672-9_16.


Lack of effective translational regulation of PLD expression and exosome biogenesis in triple-negative breast cancer cells.

Gomez-Cambronero J.

Cancer Metastasis Rev. 2018 Sep;37(2-3):491-507. doi: 10.1007/s10555-018-9753-x. Review.


Oxidized LDL phagocytosis during foam cell formation in atherosclerotic plaques relies on a PLD2-CD36 functional interdependence.

Ganesan R, Henkels KM, Wrenshall LE, Kanaho Y, Di Paolo G, Frohman MA, Gomez-Cambronero J.

J Leukoc Biol. 2018 May;103(5):867-883. doi: 10.1002/JLB.2A1017-407RR. Epub 2018 Apr 14.


Phospholipase D isoforms differentially regulate leukocyte responses to acute lung injury.

Abdulnour RE, Howrylak JA, Tavares AH, Douda DN, Henkels KM, Miller TE, Fredenburgh LE, Baron RM, Gomez-Cambronero J, Levy BD.

J Leukoc Biol. 2018 May;103(5):919-932. doi: 10.1002/JLB.3A0617-252RR. Epub 2018 Feb 13.


How miRs and mRNA deadenylases could post-transcriptionally regulate expression of tumor-promoting protein PLD.

Gomez-Cambronero J, Fite K, Miller TE.

Adv Biol Regul. 2018 May;68:107-119. doi: 10.1016/j.jbior.2017.08.002. Epub 2017 Aug 24. Review.


PLD Protein-Protein Interactions With Signaling Molecules and Modulation by PA.

Gomez-Cambronero J, Morris AJ, Henkels KM.

Methods Enzymol. 2017;583:327-357. doi: 10.1016/bs.mie.2016.09.042. Epub 2016 Nov 11.


PLD-Specific Small-Molecule Inhibitors Decrease Tumor-Associated Macrophages and Neutrophils Infiltration in Breast Tumors and Lung and Liver Metastases.

Henkels KM, Muppani NR, Gomez-Cambronero J.

PLoS One. 2016 Nov 16;11(11):e0166553. doi: 10.1371/journal.pone.0166553. eCollection 2016.


A Phosphatidic Acid (PA) conveyor system of continuous intracellular transport from cell membrane to nucleus maintains EGF receptor homeostasis.

Henkels KM, Miller TE, Ganesan R, Wilkins BA, Fite K, Gomez-Cambronero J.

Oncotarget. 2016 Jul 26;7(30):47002-47017. doi: 10.18632/oncotarget.9685.


A Repertoire of MicroRNAs Regulates Cancer Cell Starvation by Targeting Phospholipase D in a Feedback Loop That Operates Maximally in Cancer Cells.

Fite K, Elkhadragy L, Gomez-Cambronero J.

Mol Cell Biol. 2016 Jan 19;36(7):1078-89. doi: 10.1128/MCB.00711-15.


The transcription factors Slug (SNAI2) and Snail (SNAI1) regulate phospholipase D (PLD) promoter in opposite ways towards cancer cell invasion.

Ganesan R, Mallets E, Gomez-Cambronero J.

Mol Oncol. 2016 May;10(5):663-76. doi: 10.1016/j.molonc.2015.12.006. Epub 2015 Dec 19.


Down-regulation of MicroRNAs (MiRs) 203, 887, 3619 and 182 Prevents Vimentin-triggered, Phospholipase D (PLD)-mediated Cancer Cell Invasion.

Fite K, Gomez-Cambronero J.

J Biol Chem. 2016 Jan 8;291(2):719-30. doi: 10.1074/jbc.M115.686006. Epub 2015 Nov 15.


Phosphatidic Acid (PA) can Displace PPARα/LXRα Binding to The EGFR Promoter Causing its Transrepression in Luminal Cancer Cells.

Mahankali M, Farkaly T, Bedi S, Hostetler HA, Gomez-Cambronero J.

Sci Rep. 2015 Oct 23;5:15379. doi: 10.1038/srep15379.


Phosphatidic Acid Increases Epidermal Growth Factor Receptor Expression by Stabilizing mRNA Decay and by Inhibiting Lysosomal and Proteasomal Degradation of the Internalized Receptor.

Hatton N, Lintz E, Mahankali M, Henkels KM, Gomez-Cambronero J.

Mol Cell Biol. 2015 Sep;35(18):3131-44. doi: 10.1128/MCB.00286-15. Epub 2015 Jun 29.


Adenovirus entry from the apical surface of polarized epithelia is facilitated by the host innate immune response.

Kotha PL, Sharma P, Kolawole AO, Yan R, Alghamri MS, Brockman TL, Gomez-Cambronero J, Excoffon KJ.

PLoS Pathog. 2015 Mar 13;11(3):e1004696. doi: 10.1371/journal.ppat.1004696. eCollection 2015 Mar.


FASEB Science Research Conference on phospholipid cell signaling and metabolism in inflammation and cancer.

Gomez-Cambronero J.

FASEB J. 2015 Jan;29(1):5-10. doi: 10.1096/fj.15-0102ufm. No abstract available.


Two sites of action for PLD2 inhibitors: The enzyme catalytic center and an allosteric, phosphoinositide biding pocket.

Ganesan R, Mahankali M, Alter G, Gomez-Cambronero J.

Biochim Biophys Acta. 2015 Mar;1851(3):261-72. doi: 10.1016/j.bbalip.2014.12.007. Epub 2014 Dec 20.


S6K is a morphogenic protein with a mechanism involving Filamin-A phosphorylation and phosphatidic acid binding.

Henkels KM, Mallets ER, Dennis PB, Gomez-Cambronero J.

FASEB J. 2015 Apr;29(4):1299-313. doi: 10.1096/fj.14-260992. Epub 2014 Dec 15.


A non-mitotic role for Aurora kinase A as a direct activator of cell migration upon interaction with PLD, FAK and Src.

Mahankali M, Henkels KM, Speranza F, Gomez-Cambronero J.

J Cell Sci. 2015 Feb 1;128(3):516-26.


Mechanism of enzymatic reaction and protein-protein interactions of PLD from a 3D structural model.

Mahankali M, Alter G, Gomez-Cambronero J.

Cell Signal. 2015 Jan;27(1):69-81. doi: 10.1016/j.cellsig.2014.09.008. Epub 2014 Oct 12.


The molecular basis of leukocyte adhesion involving phosphatidic acid and phospholipase D.

Speranza F, Mahankali M, Henkels KM, Gomez-Cambronero J.

J Biol Chem. 2014 Oct 17;289(42):28885-97. doi: 10.1074/jbc.M114.597146. Epub 2014 Sep 2.


A river runs through it: how autophagy, senescence, and phagocytosis could be linked to phospholipase D by Wnt signaling.

Gomez-Cambronero J, Kantonen S.

J Leukoc Biol. 2014 Nov;96(5):779-84. doi: 10.1189/jlb.2VMR0214-120RR. Epub 2014 Jul 31. Review.


Thematic minireview series on phospholipase D and cancer.

Gomez-Cambronero J, Carman GM.

J Biol Chem. 2014 Aug 15;289(33):22554-6. doi: 10.1074/jbc.R114.593137. Epub 2014 Jul 2.


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

Gomez-Cambronero J.

J Biol Chem. 2014 Aug 15;289(33):22557-66. doi: 10.1074/jbc.R114.574152. Epub 2014 Jul 2. Review.


Role of c-Met/phosphatidylinositol 3-kinase (PI3k)/Akt signaling in hepatocyte growth factor (HGF)-mediated lamellipodia formation, reactive oxygen species (ROS) generation, and motility of lung endothelial cells.

Usatyuk PV, Fu P, Mohan V, Epshtein Y, Jacobson JR, Gomez-Cambronero J, Wary KK, Bindokas V, Dudek SM, Salgia R, Garcia JG, Natarajan V.

J Biol Chem. 2014 May 9;289(19):13476-91. doi: 10.1074/jbc.M113.527556. Epub 2014 Mar 14.


Phosphatidic acid, phospholipase D and tumorigenesis.

Gomez-Cambronero J.

Adv Biol Regul. 2014 Jan;54:197-206. doi: 10.1016/j.jbior.2013.08.006. Epub 2013 Sep 19.


Macrophage migration arrest due to a winning balance of Rac2/Sp1 repression over β-catenin-induced PLD expression.

Speranza FJ, Mahankali M, Gomez-Cambronero J.

J Leukoc Biol. 2013 Nov;94(5):953-62. doi: 10.1189/jlb.0313174. Epub 2013 Jul 29.


Phospholipase D (PLD) drives cell invasion, tumor growth and metastasis in a human breast cancer xenograph model.

Henkels KM, Boivin GP, Dudley ES, Berberich SJ, Gomez-Cambronero J.

Oncogene. 2013 Dec 5;32(49):5551-62. doi: 10.1038/onc.2013.207. Epub 2013 Jun 10.


Enzymatically active Rho and Rac small-GTPases are involved in the establishment of the vacuolar membrane after Toxoplasma gondii invasion of host cells.

Na RH, Zhu GH, Luo JX, Meng XJ, Cui L, Peng HJ, Chen XG, Gomez-Cambronero J.

BMC Microbiol. 2013 May 30;13:125. doi: 10.1186/1471-2180-13-125.


A new signaling pathway (JAK-Fes-phospholipase D) that is enhanced in highly proliferative breast cancer cells.

Ye Q, Kantonen S, Henkels KM, Gomez-Cambronero J.

J Biol Chem. 2013 Apr 5;288(14):9881-91. doi: 10.1074/jbc.M113.450593. Epub 2013 Feb 12.


A GEF-to-phospholipase molecular switch caused by phosphatidic acid, Rac and JAK tyrosine kinase that explains leukocyte cell migration.

Mahankali M, Henkels KM, Gomez-Cambronero J.

J Cell Sci. 2013 Mar 15;126(Pt 6):1416-28. doi: 10.1242/jcs.117960. Epub 2013 Feb 1.


Serum deprivation confers the MDA-MB-231 breast cancer line with an EGFR/JAK3/PLD2 system that maximizes cancer cell invasion.

Ye Q, Kantonen S, Gomez-Cambronero J.

J Mol Biol. 2013 Feb 22;425(4):755-66. doi: 10.1016/j.jmb.2012.11.035. Epub 2012 Dec 10.


Identification of the catalytic site of phospholipase D2 (PLD2) newly described guanine nucleotide exchange factor activity.

Mahankali M, Henkels KM, Alter G, Gomez-Cambronero J.

J Biol Chem. 2012 Nov 30;287(49):41417-31. doi: 10.1074/jbc.M112.383596. Epub 2012 Oct 3.


Increased cell growth due to a new lipase-GEF (Phospholipase D2) fastly acting on Ras.

Henkels KM, Mahankali M, Gomez-Cambronero J.

Cell Signal. 2013 Jan;25(1):198-205. doi: 10.1016/j.cellsig.2012.08.010. Epub 2012 Aug 31.


Structure analysis between the SWAP-70 RHO-GEF and the newly described PLD2-GEF.

Gomez-Cambronero J.

Small GTPases. 2012 Oct-Dec;3(4):202-8. doi: 10.4161/sgtp.20887. Epub 2012 Aug 3.


Biochemical and cellular implications of a dual lipase-GEF function of phospholipase D2 (PLD2).

Gomez-Cambronero J.

J Leukoc Biol. 2012 Sep;92(3):461-7. doi: 10.1189/jlb.0212073. Epub 2012 Jul 2. Review.


Cloning of PLD2 from baculovirus for studies in inflammatory responses.

Gomez-Cambronero J, Henkels KM.

Methods Mol Biol. 2012;861:201-25. doi: 10.1007/978-1-61779-600-5_13.


Writing a first grant proposal.

Gomez-Cambronero J, Allen LA, Cathcart MK, Justement LB, Kovacs EJ, McLeish KR, Nauseef WM.

Nat Immunol. 2012 Jan 19;13(2):105-8. doi: 10.1038/ni.2183. No abstract available.


Phospholipase D2 (PLD2) is a guanine nucleotide exchange factor (GEF) for the GTPase Rac2.

Mahankali M, Peng HJ, Henkels KM, Dinauer MC, Gomez-Cambronero J.

Proc Natl Acad Sci U S A. 2011 Dec 6;108(49):19617-22. doi: 10.1073/pnas.1114692108. Epub 2011 Nov 21.


Phospholipase D2 (PLD2) shortens the time required for myeloid leukemic cell differentiation: mechanism of action.

Di Fulvio M, Frondorf K, Henkels KM, Grunwald WC Jr, Cool D, Gomez-Cambronero J.

J Biol Chem. 2012 Jan 2;287(1):393-407. doi: 10.1074/jbc.M111.259465. Epub 2011 Nov 17.


A novel phospholipase D2-Grb2-WASp heterotrimer regulates leukocyte phagocytosis in a two-step mechanism.

Kantonen S, Hatton N, Mahankali M, Henkels KM, Park H, Cox D, Gomez-Cambronero J.

Mol Cell Biol. 2011 Nov;31(22):4524-37. doi: 10.1128/MCB.05684-11. Epub 2011 Sep 19.


The exquisite regulation of PLD2 by a wealth of interacting proteins: S6K, Grb2, Sos, WASp and Rac2 (and a surprise discovery: PLD2 is a GEF).

Gomez-Cambronero J.

Cell Signal. 2011 Dec;23(12):1885-95. doi: 10.1016/j.cellsig.2011.06.017. Epub 2011 Jun 29. Review.


The dual effect of Rac2 on phospholipase D2 regulation that explains both the onset and termination of chemotaxis.

Peng HJ, Henkels KM, Mahankali M, Marchal C, Bubulya P, Dinauer MC, Gomez-Cambronero J.

Mol Cell Biol. 2011 Jun;31(11):2227-40. doi: 10.1128/MCB.01348-10. Epub 2011 Mar 28.


The mechanism of cell membrane ruffling relies on a phospholipase D2 (PLD2), Grb2 and Rac2 association.

Mahankali M, Peng HJ, Cox D, Gomez-Cambronero J.

Cell Signal. 2011 Aug;23(8):1291-8. doi: 10.1016/j.cellsig.2011.03.010. Epub 2011 Mar 16.


Cell invasion of highly metastatic MTLn3 cancer cells is dependent on phospholipase D2 (PLD2) and Janus kinase 3 (JAK3).

Henkels KM, Farkaly T, Mahankali M, Segall JE, Gomez-Cambronero J.

J Mol Biol. 2011 May 20;408(5):850-62. doi: 10.1016/j.jmb.2011.03.017. Epub 2011 Mar 22.


Evidence for two CRIB domains in phospholipase D2 (PLD2) that the enzyme uses to specifically bind to the small GTPase Rac2.

Peng HJ, Henkels KM, Mahankali M, Dinauer MC, Gomez-Cambronero J.

J Biol Chem. 2011 May 6;286(18):16308-20. doi: 10.1074/jbc.M110.206672. Epub 2011 Mar 4.


IL-8-induced neutrophil chemotaxis is mediated by Janus kinase 3 (JAK3).

Henkels KM, Frondorf K, Gonzalez-Mejia ME, Doseff AL, Gomez-Cambronero J.

FEBS Lett. 2011 Jan 3;585(1):159-66. doi: 10.1016/j.febslet.2010.11.031. Epub 2010 Nov 21.

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