17344213

Source:http://linkedlifedata.com/resource/pubmed/id/17344213

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Predicate	Object
rdf:type	pubmed:Citation
lifeskim:mentions	umls-concept:C0000887, umls-concept:C0030807, umls-concept:C0037083, umls-concept:C0086982, umls-concept:C0113216, umls-concept:C0205314, umls-concept:C0679622, umls-concept:C1414170, umls-concept:C1710082, umls-concept:C1880022
pubmed:issue	18
pubmed:dateCreated	2007-4-30
pubmed:abstractText	Although it is accepted that pemphigus antibody binding to keratinocytes (KCs) evokes an array of intracellular biochemical events resulting in cell detachment and death, the triggering events remain obscure. It has been postulated that the binding of pemphigus vulgaris IgG (PVIgG) to KCs induces "desmosomal" signaling. Because in contrast to integrins and classical cadherins, desmoglein (Dsg) molecules are not known to elicit intracellular signaling, and because PV patients also produce non-Dsg autoantibodies, we investigated the roles of both Dsg and non-desmoglein PV antigens. The time course studies of KCs treated with PVIgG demonstrated that the activity of Src peaked at 30 min, EGF receptor kinase (EGFRK) at 60 min, and p38 MAPK at 240 min. The Src inhibitor PP2 decreased EGFRK and p38 activities by approximately 45 and 30%, respectively, indicating that in addition to Src, PVIgG evokes other triggering events. The shrinkage of KCs (cell volume reduction) became significant at 120 min, keratin aggregation at 240 min, and an increase of TUNEL positivity at 360 min. Pretreatment of KCs with PP2 blocked PVIgG-dependent cell shrinkage and keratin aggregation by approximately 50% and TUNEL positivity by approximately 25%. The p38 MAPK inhibitor PD169316 inhibited these effects by approximately 15, 20, and 70%, respectively. Transfection of KCs with small interfering RNAs that silenced expression of Dsg1 and/or Dsg3 proteins, blocked approximately 50% of p38 MAPK activity but did not significantly alter the PVIgG-dependent rise in Src and EGFRK activities. These results indicate that activation of p38 MAPK is a late signaling step associated with collapse of the cytoskeleton and disassembly of desmosomes caused by upstream events involving Src and EGFRK. Therefore, the early acantholytic events are triggered by non-Dsg antibodies.
pubmed:language	eng
pubmed:journal	http://linkedlifedata.com/resource/pubmed/journal/2985121R
pubmed:citationSubset	IM
pubmed:chemical	http://linkedlifedata.com/resource/pubmed/chemical/AG 1879, http://linkedlifedata.com/resource/pubmed/chemical/Antigens, http://linkedlifedata.com/resource/pubmed/chemical/Autoantibodies, http://linkedlifedata.com/resource/pubmed/chemical/DSG1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/DSG2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Desmoglein 1, http://linkedlifedata.com/resource/pubmed/chemical/Desmoglein 2, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles, http://linkedlifedata.com/resource/pubmed/chemical/Keratins, http://linkedlifedata.com/resource/pubmed/chemical/PD 169316, http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines, http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor, http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein..., http://linkedlifedata.com/resource/pubmed/chemical/src-Family Kinases
pubmed:status	MEDLINE
pubmed:month	May
pubmed:issn	0021-9258
pubmed:author	pubmed-author:ArredondoJuanJ, pubmed-author:ChernyavskyAlex IAI, pubmed-author:GrandoSergei ASA, pubmed-author:KitajimaYasuoY, pubmed-author:Sato-NagaiMikiM
pubmed:issnType	Print
pubmed:day	4
pubmed:volume	282
pubmed:owner	NLM
pubmed:authorsComplete	Y
pubmed:pagination	13804-12
pubmed:dateRevised	2009-11-19
pubmed:meshHeading	pubmed-meshheading:17344213-Acantholysis, pubmed-meshheading:17344213-Antigens, pubmed-meshheading:17344213-Autoantibodies, pubmed-meshheading:17344213-Cell Adhesion, pubmed-meshheading:17344213-Cell Shape, pubmed-meshheading:17344213-Cells, Cultured, pubmed-meshheading:17344213-Cytoskeleton, pubmed-meshheading:17344213-DNA Fragmentation, pubmed-meshheading:17344213-Desmoglein 1, pubmed-meshheading:17344213-Desmoglein 2, pubmed-meshheading:17344213-Desmosomes, pubmed-meshheading:17344213-Enzyme Inhibitors, pubmed-meshheading:17344213-Humans, pubmed-meshheading:17344213-Imidazoles, pubmed-meshheading:17344213-Keratinocytes, pubmed-meshheading:17344213-Keratins, pubmed-meshheading:17344213-MAP Kinase Signaling System, pubmed-meshheading:17344213-Pemphigus, pubmed-meshheading:17344213-Pyrimidines, pubmed-meshheading:17344213-Receptor, Epidermal Growth Factor, pubmed-meshheading:17344213-Time Factors, pubmed-meshheading:17344213-p38 Mitogen-Activated Protein Kinases, pubmed-meshheading:17344213-src-Family Kinases
pubmed:year	2007
pubmed:articleTitle	Desmoglein versus non-desmoglein signaling in pemphigus acantholysis: characterization of novel signaling pathways downstream of pemphigus vulgaris antigens.
pubmed:affiliation	Department of Dermatology, University of California, Davis, California 95816, USA.
pubmed:publicationType	Journal Article, Research Support, Non-U.S. Gov't