New concepts in phospholipase D signaling in inflammation and cancer.

TheScientificWorldJournal
Julian Gomez-Cambronero

Abstract

Phospholipase D (PLD) catalyzes the hydrolysis of phosphatidylcholine to generate the lipid second messenger phosphatidic acid (PA) and choline. PLD regulation in cells falls into two major signaling categories. One is via growth factors/mitogens, such as EGF, PDGF, insulin, and serum, and implicates tyrosine kinases; the other is via the small GTPase proteins Arf and Rho. We summarize here our lab's and other groups' contributions to those pathways and introduce several novel concepts. For the mitogen-induced signaling, new data indicate that an increase in cell transformation in PLD2-overexpressing cells is due to an increase of de novo DNA synthesis induced by PLD2, with the specific tyrosine residues involved in those functions being Y179 and Y511. Recent research has also implicated Grb2 in tyrosine phosphorylation of PLD2 that also involves Sos and the ERK pathway. The targets of phosphorylation within the PLD2 molecule that are key to its regulation have recently been precisely mapped. They are Y296, Y415, and Y511 and the responsible kinases are, respectively, EGFR, JAK3, and Src. Y296 is an inhibitory site and its phosphorylation explains the low PLD2 activity that exists in low-invasive MCF-7 breast cancer cells. Adva...Continue Reading

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Citations

Jul 4, 2012·Journal of Leukocyte Biology·Julian Gomez-Cambronero
Jan 5, 2013·Journal of Lipid Research·Senthil N ArunWendy B Bollag
Apr 13, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Nicklaus SparrowCristina Fernandez-Valle
Apr 29, 2014·BioMed Research International·Yamila B GándolaLorena Gonzalez
Aug 23, 2011·Immunopharmacology and Immunotoxicology·Li-Qiong CaiLing Zhu
Dec 20, 2011·Biochimica Et Biophysica Acta·Cristina CadenasJan G Hengstler
Jan 4, 2012·Progress in Lipid Research·Jin-Hyeok JangSung Ho Ryu
Nov 24, 2011·The International Journal of Biochemistry & Cell Biology·Young Hoon Jang, Do Sik Min
Dec 6, 2011·Experimental Eye Research·Wanwen Lan, Louis Tong
Jul 7, 2012·Journal of Cellular Physiology·M Luísa DóriaLuisa A Helguero
Oct 10, 2013·Advances in Biological Regulation·Julian Gomez-Cambronero
Oct 7, 2014·ELife·Richard K HiteRoderick MacKinnon
Dec 20, 2014·Experimental & Molecular Medicine·Songyi HanYunjin Jung
Aug 2, 2014·Journal of Leukocyte Biology·Julian Gomez-Cambronero, Samuel Kantonen
Oct 15, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Mohamad El OstaYusuf A Hannun
Jun 19, 2020·International Journal of Molecular Sciences·Vidyani SuryadevaraViswanathan Natarajan
Nov 10, 2011·Toxins·Olga Meiri ChaimSilvio Sanches Veiga
Oct 14, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ramya GanesanJulian Gomez-Cambronero
Oct 21, 2020·Biomolecules·Robert M SchilkeMatthew D Woolard

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