000140611 001__ 140611
000140611 005__ 20240321220837.0
000140611 0247_ $$2doi$$a10.1084/jem.20171438
000140611 0247_ $$2pmid$$apmid:30819724
000140611 0247_ $$2pmc$$apmc:PMC6446863
000140611 0247_ $$2ISSN$$a0022-1007
000140611 0247_ $$2ISSN$$a1540-9358
000140611 0247_ $$2ISSN$$a1540-9538
000140611 0247_ $$2altmetric$$aaltmetric:56715047
000140611 037__ $$aDZNE-2020-06933
000140611 041__ $$aEnglish
000140611 082__ $$a610
000140611 1001_ $$aMentrup, Torben$$b0
000140611 245__ $$aAtherogenic LOX-1 signaling is controlled by SPPL2-mediated intramembrane proteolysis.
000140611 260__ $$aNew York, NY$$bRockefeller Univ. Press$$c2019
000140611 264_1 $$2Crossref$$3online$$bRockefeller University Press$$c2019-02-28
000140611 264_1 $$2Crossref$$3print$$bRockefeller University Press$$c2019-04-01
000140611 3367_ $$2DRIVER$$aarticle
000140611 3367_ $$2DataCite$$aOutput Types/Journal article
000140611 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1589472013_7797
000140611 3367_ $$2BibTeX$$aARTICLE
000140611 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000140611 3367_ $$00$$2EndNote$$aJournal Article
000140611 520__ $$aThe lectin-like oxidized LDL receptor 1 (LOX-1) is a key player in the development of atherosclerosis. LOX-1 promotes endothelial activation and dysfunction by mediating uptake of oxidized LDL and inducing pro-atherogenic signaling. However, little is known about modulators of LOX-1-mediated responses. Here, we show that the function of LOX-1 is controlled proteolytically. Ectodomain shedding by the metalloprotease ADAM10 and lysosomal degradation generate membrane-bound N-terminal fragments (NTFs), which we identified as novel substrates of the intramembrane proteases signal peptide peptidase-like 2a and b (SPPL2a/b). SPPL2a/b control cellular LOX-1 NTF levels which, following self-association via their transmembrane domain, can activate MAP kinases in a ligand-independent manner. This leads to an up-regulation of several pro-atherogenic and pro-fibrotic targets including ICAM-1 and the connective tissue growth factor CTGF. Consequently, SPPL2a/b-deficient mice, which accumulate LOX-1 NTFs, develop larger and more advanced atherosclerotic plaques than controls. This identifies intramembrane proteolysis by SPPL2a/b as a novel atheroprotective mechanism via negative regulation of LOX-1 signaling.
000140611 536__ $$0G:(DE-HGF)POF3-342$$a342 - Disease Mechanisms and Model Systems (POF3-342)$$cPOF3-342$$fPOF III$$x0
000140611 542__ $$2Crossref$$i2019-02-28$$uhttp://www.rupress.org/terms/
000140611 542__ $$2Crossref$$i2019-09-30$$uhttps://creativecommons.org/licenses/by-nc-sa/4.0/
000140611 588__ $$aDataset connected to CrossRef, PubMed,
000140611 650_2 $$2MeSH$$aADAM10 Protein: metabolism
000140611 650_2 $$2MeSH$$aAmyloid Precursor Protein Secretases: metabolism
000140611 650_2 $$2MeSH$$aAnimals
000140611 650_2 $$2MeSH$$aAspartic Acid Endopeptidases: antagonists & inhibitors
000140611 650_2 $$2MeSH$$aAspartic Acid Endopeptidases: genetics
000140611 650_2 $$2MeSH$$aAspartic Acid Endopeptidases: metabolism
000140611 650_2 $$2MeSH$$aAtherosclerosis: metabolism
000140611 650_2 $$2MeSH$$aDipeptides: pharmacology
000140611 650_2 $$2MeSH$$aEndothelial Cells: metabolism
000140611 650_2 $$2MeSH$$aHEK293 Cells
000140611 650_2 $$2MeSH$$aHeLa Cells
000140611 650_2 $$2MeSH$$aHumans
000140611 650_2 $$2MeSH$$aMembrane Proteins: genetics
000140611 650_2 $$2MeSH$$aMembrane Proteins: metabolism
000140611 650_2 $$2MeSH$$aMice
000140611 650_2 $$2MeSH$$aMice, Inbred C57BL
000140611 650_2 $$2MeSH$$aMice, Knockout
000140611 650_2 $$2MeSH$$aProteolysis
000140611 650_2 $$2MeSH$$aScavenger Receptors, Class E: genetics
000140611 650_2 $$2MeSH$$aScavenger Receptors, Class E: metabolism
000140611 650_2 $$2MeSH$$aTransfection
000140611 7001_ $$aTheodorou, Kosta$$b1
000140611 7001_ $$aCabrera-Cabrera, Florencia$$b2
000140611 7001_ $$aHelbig, Andreas O$$b3
000140611 7001_ $$aHapp, Kathrin$$b4
000140611 7001_ $$aGijbels, Marion$$b5
000140611 7001_ $$aGradtke, Ann-Christine$$b6
000140611 7001_ $$aRabe, Björn$$b7
000140611 7001_ $$0P:(DE-2719)2810765$$aFukumori, Akio$$b8$$udzne
000140611 7001_ $$0P:(DE-2719)2000023$$aSteiner, Harald$$b9$$udzne
000140611 7001_ $$aTholey, Andreas$$b10
000140611 7001_ $$0P:(DE-2719)2000007$$aFluhrer, Regina$$b11$$udzne
000140611 7001_ $$aDonners, Marjo$$b12
000140611 7001_ $$0P:(DE-HGF)0$$aSchröder, Bernd$$b13$$eCorresponding author
000140611 77318 $$2Crossref$$3journal-article$$a10.1084/jem.20171438$$b : Rockefeller University Press, 2019-02-28$$n4$$p807-830$$tJournal of Experimental Medicine$$v216$$x0022-1007$$y2019
000140611 773__ $$0PERI:(DE-600)1477240-1$$a10.1084/jem.20171438$$gVol. 216, no. 4, p. 807 - 830$$n4$$p807-830$$q216:4<807 - 830$$tJournal of experimental medicine$$v216$$x0022-1007$$y2019
000140611 8567_ $$2Pubmed Central$$uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446863
000140611 909CO $$ooai:pub.dzne.de:140611$$pVDB
000140611 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2810765$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b8$$kDZNE
000140611 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2000023$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b9$$kDZNE
000140611 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2000007$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b11$$kDZNE
000140611 9131_ $$0G:(DE-HGF)POF3-342$$1G:(DE-HGF)POF3-340$$2G:(DE-HGF)POF3-300$$aDE-HGF$$bForschungsbereich Gesundheit$$lErkrankungen des Nervensystems$$vDisease Mechanisms and Model Systems$$x0
000140611 9141_ $$y2019
000140611 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bJ EXP MED : 2021$$d2022-11-13
000140611 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2022-11-13
000140611 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2022-11-13
000140611 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2022-11-13
000140611 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2022-11-13
000140611 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2022-11-13
000140611 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2022-11-13
000140611 915__ $$0StatID:(DE-HGF)9915$$2StatID$$aIF >= 15$$bJ EXP MED : 2021$$d2022-11-13
000140611 9201_ $$0I:(DE-2719)1110000-1$$kAG Steiner$$lBiochemistry of γ-Secretase$$x0
000140611 9201_ $$0I:(DE-2719)1110000-2$$kAG Fluhrer$$lSignal Peptide Peptidases as Models for γ-Secretase$$x1
000140611 980__ $$ajournal
000140611 980__ $$aVDB
000140611 980__ $$aI:(DE-2719)1110000-1
000140611 980__ $$aI:(DE-2719)1110000-2
000140611 980__ $$aUNRESTRICTED
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/eurheartj/eht532$$o10.1093/eurheartj/eht532
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.4049/jimmunol.1203421$$o10.4049/jimmunol.1203421
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.bbrc.2009.03.154$$o10.1016/j.bbrc.2009.03.154
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.ceb.2013.05.003$$o10.1016/j.ceb.2013.05.003
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.febslet.2011.08.043$$o10.1016/j.febslet.2011.08.043
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1084/jem.20121072$$o10.1084/jem.20121072
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1084/jem.20121076$$o10.1084/jem.20121076
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.5551/jat1994.7.14$$o10.5551/jat1994.7.14
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1161/CIRCRESAHA.114.302937$$o10.1161/CIRCRESAHA.114.302937
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1152/ajpheart.00917.2009$$o10.1152/ajpheart.00917.2009
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1161/01.HYP.0000179045.95915.b0$$o10.1161/01.HYP.0000179045.95915.b0
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1161/01.ATV.0000162173.27682.7b$$o10.1161/01.ATV.0000162173.27682.7b
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1074/jbc.275.17.12633$$o10.1074/jbc.275.17.12633
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s11010-014-2068-5$$o10.1007/s11010-014-2068-5
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1097/FJC.0000000000000035$$o10.1097/FJC.0000000000000035
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.3892/mmr.2016.5735$$o10.3892/mmr.2016.5735
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/19083$$o10.1038/19083
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.vph.2016.05.013$$o10.1016/j.vph.2016.05.013
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1042/BST0370173$$o10.1042/BST0370173
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1078/0171-9335-00122$$o10.1078/0171-9335-00122
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/ncb1450$$o10.1038/ncb1450
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/ncb1440$$o10.1038/ncb1440
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/S0021-9150(98)00263-9$$o10.1016/S0021-9150(98)00263-9
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1161/CIRCRESAHA.115.306301$$o10.1161/CIRCRESAHA.115.306301
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1186/s12974-016-0479-9$$o10.1186/s12974-016-0479-9
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.atherosclerosis.2016.06.011$$o10.1016/j.atherosclerosis.2016.06.011
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1146/annurev.pharmtox.48.113006.094830$$o10.1146/annurev.pharmtox.48.113006.094830
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1161/CIRCULATIONAHA.104.468397$$o10.1161/CIRCULATIONAHA.104.468397
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1161/CIRCRESAHA.115.307611$$o10.1161/CIRCRESAHA.115.307611
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/cvr/cvn110$$o10.1093/cvr/cvn110
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1074/jbc.M708820200$$o10.1074/jbc.M708820200
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/ki.2009.234$$o10.1038/ki.2009.234
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.4049/jimmunol.1403171$$o10.4049/jimmunol.1403171
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1161/01.RES.0000174286.73200.d4$$o10.1161/01.RES.0000174286.73200.d4
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1172/jci.insight.95890$$o10.1172/jci.insight.95890
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1161/01.CIR.99.24.3110$$o10.1161/01.CIR.99.24.3110
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/S0021-9150(01)00587-1$$o10.1016/S0021-9150(01)00587-1
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/227680a0$$o10.1038/227680a0
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.tibs.2015.04.001$$o10.1016/j.tibs.2015.04.001
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/ncomms8333$$o10.1038/ncomms8333
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1161/01.CIR.101.25.2889$$o10.1161/01.CIR.101.25.2889
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1161/01.CIR.0000047276.52039.FB$$o10.1161/01.CIR.0000047276.52039.FB
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1111/j.1471-4159.2011.07248.x$$o10.1111/j.1471-4159.2011.07248.x
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1161/ATVBAHA.116.307613$$o10.1161/ATVBAHA.116.307613
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/gt.2011.133$$o10.1038/gt.2011.133
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/S0022-1759(98)00204-X$$o10.1016/S0022-1759(98)00204-X
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.yexcr.2007.01.007$$o10.1016/j.yexcr.2007.01.007
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/S0006-291X(03)00308-5$$o10.1016/S0006-291X(03)00308-5
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1152/ajpcell.00513.2008$$o10.1152/ajpcell.00513.2008
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1152/ajpcell.00483.2009$$o10.1152/ajpcell.00483.2009
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1161/CIRCRESAHA.107.149724$$o10.1161/CIRCRESAHA.107.149724
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1111/tra.12287$$o10.1111/tra.12287
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.atherosclerosis.2008.04.002$$o10.1016/j.atherosclerosis.2008.04.002
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1161/01.ATV.20.3.715$$o10.1161/01.ATV.20.3.715
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1242/jcs.020917$$o10.1242/jcs.020917
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1161/ATVBAHA.116.308682$$o10.1161/ATVBAHA.116.308682
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1155/2013/716325$$o10.1155/2013/716325
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.3109/08830185.2013.777065$$o10.3109/08830185.2013.777065
000140611 999C5 $$2Crossref$$oRadons 1992$$y1992
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.cytogfr.2004.03.004$$o10.1016/j.cytogfr.2004.03.004
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/srep25550$$o10.1038/srep25550
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1161/CIRCRESAHA.116.310293$$o10.1161/CIRCRESAHA.116.310293
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/386073a0$$o10.1038/386073a0
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1084/jem.20121069$$o10.1084/jem.20121069
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.bbrc.2014.07.051$$o10.1016/j.bbrc.2014.07.051
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1128/MCB.00038-14$$o10.1128/MCB.00038-14
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1515/bc.2010.062$$o10.1515/bc.2010.062
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/nar/18.16.4945$$o10.1093/nar/18.16.4945
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1242/jcs.01582$$o10.1242/jcs.01582
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nprot.2006.468$$o10.1038/nprot.2006.468
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1186/1478-811X-9-14$$o10.1186/1478-811X-9-14
000140611 999C5 $$2Crossref$$oSteinberg 1989$$y1989
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/srep16740$$o10.1038/srep16740
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/s41598-017-10549-x$$o10.1038/s41598-017-10549-x
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.jprot.2014.09.027$$o10.1016/j.jprot.2014.09.027
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.ajpath.2014.11.028$$o10.1016/j.ajpath.2014.11.028
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.bbamem.2013.03.033$$o10.1016/j.bbamem.2013.03.033
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1161/HYPERTENSIONAHA.112.200659$$o10.1161/HYPERTENSIONAHA.112.200659
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.carpath.2010.08.007$$o10.1016/j.carpath.2010.08.007
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1073/pnas.86.2.612$$o10.1073/pnas.86.2.612
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1074/jbc.M113.517540$$o10.1074/jbc.M113.517540
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s00018-012-1194-z$$o10.1007/s00018-012-1194-z
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.atherosclerosis.2017.10.016$$o10.1016/j.atherosclerosis.2017.10.016
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1194/jlr.M015156$$o10.1194/jlr.M015156
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1002/iub.598$$o10.1002/iub.598
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.2741/1722$$o10.2741/1722
000140611 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1084/jem.20090866$$o10.1084/jem.20090866