{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:24:18Z","timestamp":1790177058061,"version":"4.1.0"},"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2013,8,23]],"date-time":"2013-08-23T00:00:00Z","timestamp":1377216000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0073173","type":"journal-article","created":{"date-parts":[[2013,8,23]],"date-time":"2013-08-23T17:07:04Z","timestamp":1377277624000},"page":"e73173","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":21,"title":["The Role of Phospholipase D in Modulating the MTOR Signaling Pathway in Polycystic Kidney Disease"],"prefix":"10.1371","volume":"8","author":[{"given":"Yang","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres","family":"K\u00e4ch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urs","family":"Ziegler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert C. M.","family":"Ong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren P.","family":"Wallace","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Arcaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas L.","family":"Serra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2013,8,23]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/ng1076","article-title":"Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells","volume":"33","author":"SM Nauli","year":"2003","journal-title":"Nat Genet"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1002\/path.2392","article-title":"Tight junction composition is altered in the epithelium of polycystic kidneys","volume":"216","author":"ASL Yu","year":"2008","journal-title":"J Pathol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"5466","DOI":"10.1073\/pnas.0509694103","article-title":"The mTOR pathway is regulated by polycystin-1, and its inhibition reverses renal cystogenesis in polycystic kidney disease","volume":"103","author":"JM Shillingford","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1038\/nature04869","article-title":"Ras, PI(3)K and mTOR signalling controls tumour cell growth","volume":"441","author":"RJ Shaw","year":"2006","journal-title":"Nature"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/nature11861","article-title":"mTOR is a key modulator of ageing and age-related disease","volume":"493","author":"SC Johnson","year":"2013","journal-title":"Nature"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.cell.2006.01.016","article-title":"TOR signaling in growth and metabolism","volume":"124","author":"S Wullschleger","year":"2006","journal-title":"Cell"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.cellsig.2009.01.012","article-title":"Mammalian target of rapamycin complex 1: Signalling inputs, substrates and feedback mechanisms","volume":"21","author":"EA Dunlop","year":"2009","journal-title":"Cell Signal"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"40386","DOI":"10.1074\/jbc.M111.282590","article-title":"The mTOR (Mammalian Target of Rapamycin) Kinase Maintains Integrity of mTOR Complex 2","volume":"286","author":"CH Chen","year":"2011","journal-title":"J Biol Chem"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1942","DOI":"10.1126\/science.1066015","article-title":"Phosphatidic acid-mediated mitogenic activation of mTOR signaling","volume":"294","author":"YM Fang","year":"2001","journal-title":"Science"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/j.bbalip.2009.03.013","article-title":"Emerging findings from studies of phospholipase D in model organisms (and a short update on phosphatidic acid effectors)","volume":"1791","author":"P Raghu","year":"2009","journal-title":"Biochim Biophys Acta"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1128\/MCB.00782-08","article-title":"Regulation of mTORC1 and mTORC2 Complex Assembly by Phosphatidic Acid: Competition with Rapamycin","volume":"29","author":"A Toschi","year":"2009","journal-title":"Mol Cell Biol"},{"key":"ref12","first-page":"134","article-title":"Constitutive activation with overexpression of the mTORC2-phospholipase D1 pathway in uterine leiomyosarcoma and STUMP: morphoproteomic analysis with therapeutic implications","volume":"4","author":"S Dhingra","year":"2011","journal-title":"Int J Clinical Experimental Pathology"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1006\/bbrc.2000.3719","article-title":"Increased activity and intranuclear expression of phospholipase D2 in human renal cancer","volume":"278","author":"YT Zhao","year":"2000","journal-title":"Biochem Biophys Res Commun"},{"key":"ref14","first-page":"13","article-title":"Morphoproteomic analysis reveals an overexpressed and constitutively activated phospholipase D1-mTORC2 pathway in endometrial carcinoma","volume":"4","author":"Q Shen","year":"2011","journal-title":"Int J Clinical Experimental Pathology"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1126\/science.1193497","article-title":"Autophagy and Metabolism","volume":"330","author":"JD Rabinowitz","year":"2010","journal-title":"Science"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1158\/1535-7163.MCT-11-0047","article-title":"The Role of Autophagy in Cancer: Therapeutic Implications","volume":"10","author":"ZNJ Yang","year":"2011","journal-title":"Mol Cancer Ther"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1016\/j.febslet.2010.01.017","article-title":"mTOR regulation of autophagy","volume":"584","author":"CH Jung","year":"2010","journal-title":"FEBS Lett"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"F1235","DOI":"10.1152\/ajprenal.00348.2010","article-title":"Hypoxia-inducible factor-1alpha (HIF-1alpha) and autophagy in polycystic kidney disease (PKD)","volume":"300","author":"F Belibi","year":"2011","journal-title":"Am J Physiol Renal Physiol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"322","DOI":"10.4161\/auto.6.3.11625","article-title":"Targeting the prodeath and prosurvival functions of autophagy as novel therapeutic strategies in cancer","volume":"6","author":"KN Dalby","year":"2010","journal-title":"Autophagy"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1038\/ki.1996.445","article-title":"Chloride and fluid secretion by cultured human polycystic kidney cells","volume":"50","author":"DP Wallace","year":"1996","journal-title":"Kidney Int"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/sj.ki.5002229","article-title":"Hyperproliferation of PKD1 cystic cells is induced by insulin-like growth factor-1 activation of the Ras\/Raf signalling system","volume":"72","author":"E Parker","year":"2007","journal-title":"Kidney Int"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1093\/ndt\/11.supp6.46","article-title":"Rat models of autosomal dominant polycystic kidney disease","volume":"11","author":"N Gretz","year":"1996","journal-title":"Nephrol Dial Transplant"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"F397","DOI":"10.1152\/ajprenal.00310.2002","article-title":"Immortalized epithelial cells from human autosomal dominant polycystic kidney cysts","volume":"285","author":"M Loghman-Adham","year":"2003","journal-title":"Am J Physiol Renal Physiol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"4267","DOI":"10.1158\/1078-0432.CCR-08-0102","article-title":"Honokiol suppresses survival signals mediated by Ras-dependent phospholipase D activity in human cancer cells","volume":"14","author":"A Garcia","year":"2008","journal-title":"Clin Cancer Res"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"4267","DOI":"10.1158\/1078-0432.CCR-08-0102","article-title":"Honokiol suppresses survival signals mediated by Ras-dependent phospholipase D activity in human cancer cells","volume":"14","author":"A Garcia","year":"2008","journal-title":"Clin Cancer Res"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nchembio.140","article-title":"Design of isoform-selective phospholipase D inhibitors that modulate cancer cell invasiveness","volume":"5","author":"SA Scott","year":"2009","journal-title":"Nat Chem Biol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1128\/MCB.00782-08","article-title":"Regulation of mTORC1 and mTORC2 complex assembly by phosphatidic acid: competition with rapamycin","volume":"29","author":"A Toschi","year":"2009","journal-title":"Mol Cell Biol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1681\/ASN.2011040340","article-title":"Dose-Dependent Effects of Sirolimus on mTOR Signaling and Polycystic Kidney Disease","volume":"23","author":"Z Novalic","year":"2012","journal-title":"J Am Soc Nephrol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"F1597","DOI":"10.1152\/ajprenal.00430.2009","article-title":"Pulse mTOR inhibitor treatment effectively controls cyst growth but leads to severe parenchymal and glomerular hypertrophy in rat polycystic kidney disease","volume":"297","author":"M Wu","year":"2009","journal-title":"Am J Physiol Renal Physiol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1038\/ki.2010.250","article-title":"Sirolimus attenuates disease progression in an orthologous mouse model of human autosomal dominant polycystic kidney disease","volume":"78","author":"I Zafar","year":"2010","journal-title":"Kidney Int"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1056\/NEJMoa0907419","article-title":"Sirolimus and Kidney Growth in Autosomal Dominant Polycystic Kidney Disease","volume":"363","author":"AL Serra","year":"2010","journal-title":"N Engl J Med"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1056\/NEJMoa1003491","article-title":"Everolimus in Patients with Autosomal Dominant Polycystic Kidney Disease (vol 363, pg 830, 2010)","volume":"363","author":"G Walz","year":"2010","journal-title":"N Engl J Med"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"3937","DOI":"10.1038\/sj.onc.1206565","article-title":"Phospholipase D confers rapamycin resistance in human breast cancer cells","volume":"22","author":"YH Chen","year":"2003","journal-title":"Oncogene"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/ng1494","article-title":"Dysregulation of the TSC-mTOR pathway in human disease","volume":"37","author":"K Inoki","year":"2005","journal-title":"Nat Genet"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"F1005","DOI":"10.1152\/ajprenal.00243.2011","article-title":"Tolvaptan inhibits ERK-dependent cell proliferation. p. Cl(-) secretion, and in vitro cyst growth of human ADPKD cells stimulated by vasopressin","volume":"301","author":"GA Reif","year":"2011","journal-title":"Am J Physiol Renal Physiol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1083\/jcb.201006173","article-title":"The cell biology of polycystic kidney disease","volume":"191","author":"HC Chapin","year":"2010","journal-title":"J Cell Biol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1755-8417-2-6","article-title":"Emerging evidence of a link between the polycystins and the mTOR pathways","volume":"2","author":"A Boletta","year":"2009","journal-title":"Pathogenetics"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1096\/fj.06-6652com","article-title":"Phospholipase D2-derived phosphatidic acid binds to and activates ribosomal p70 S6 kinase independently of mTOR","volume":"21","author":"N Lehman","year":"2007","journal-title":"FASEB J"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1100\/tsw.2010.116","article-title":"New Concepts in Phospholipase D Signaling in Inflammation and Cancer","volume":"10","author":"J Gomez-Cambronero","year":"2010","journal-title":"Thescientificworldjournal"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1038\/nrc3379","article-title":"Phospholipase signalling networks in cancer","volume":"12","author":"JB Park","year":"2012","journal-title":"Nat Rev Cancer"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.plipres.2011.12.003","article-title":"Understanding of the roles of phospholipase D and phosphatidic acid through their binding partners","volume":"51","author":"JH Jang","year":"2012","journal-title":"Prog Lipid Res"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1038\/emboj.2009.377","article-title":"Crosstalk between apoptosis and autophagy within the Beclin 1 interactome","volume":"29","author":"MC Maiuri","year":"2010","journal-title":"EMBO J"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/nrclinonc.2011.71","article-title":"Autophagy as a target for anticancer therapy","volume":"8","author":"F Janku","year":"2011","journal-title":"Nat Rev Clin Oncol"},{"key":"ref44","first-page":"R59022","article-title":"Diacylglycerol kinase inhibitor","author":"T Takita","year":"2011","journal-title":"Diacylglycerol kinase inhibitor"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1038\/ncomms1144","article-title":"The phospholipase D1 pathway modulates macroautophagy","volume":"1","author":"C Dall\u2019Armi","year":"2010","journal-title":"Nat Commun"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.biochi.2007.08.014","article-title":"Regulation of macroautophagy by mTOR and Beclin 1 complexes","volume":"90","author":"S Pattingre","year":"2008","journal-title":"Biochimie"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20071427","article-title":"The regulation and function of Class III PI3Ks: novel roles for Vps34","volume":"410","author":"JM Backer","year":"2008","journal-title":"Biochem J"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1681\/ASN.2012040367","article-title":"Folate-conjugated rapamycin slows progression of polycystic kidney disease","volume":"23","author":"JM Shillingford","year":"2012","journal-title":"J Am Soc Nephrol"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0073173","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,7,21]],"date-time":"2019-07-21T17:40:16Z","timestamp":1563730816000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0073173"}},"subtitle":[],"editor":[{"given":"Leighton\u00a0R","family":"James","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2013,8,23]]},"references-count":48,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2013,8,23]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0073173","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,8,23]]}}}