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Article: Requirement of TGF-β Receptor-Dependent Activation of c-Jun N-Terminal Kinases (JNKs)/Stress-Activated Protein Kinases (Sapks) for TGF-β Up-Regulation of the Urokinase-Type Plasminogen Activator Receptor

TitleRequirement of TGF-β Receptor-Dependent Activation of c-Jun N-Terminal Kinases (JNKs)/Stress-Activated Protein Kinases (Sapks) for TGF-β Up-Regulation of the Urokinase-Type Plasminogen Activator Receptor
Authors
Issue Date2004
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/31010
Citation
Journal Of Cellular Physiology, 2004, v. 199 n. 2, p. 284-292 How to Cite?
AbstractWe have previously demonstrated that activation of the Ras/Mapk pathways is required for transforming growth factor β (TGF-β) induction of TGF-β 1 expression. Here we examined the role of the Ras/Mapk pathways in TGF-β induction of urokinase-type plasminogen activator receptor (uPAR) expression in untransformed intestinal epithelial cells (IECs). TGF-β activated the stress-activated protein kinases (Sapk)/c-Jun N-terminal kinases (JNKs) within 5-10 min, an effect that preceeded TGF-β induction of uPAR expression in these cells. TGF-β induction of both JNK1 activity and JunD phosphorylation was blocked by expression of a dominant-negative mutant of the type II TGF-β receptor (DN TβRII), a dominant-negative mutant of MKK4 (DN MKK4), or a dominant-negative mutant of Ras (RasN17), or by the addition of the JNK inhibitor SP600125. TGF-β also induced AP-1 complex formation at the distal AP-1 site (-184 to -178) of the uPAR promoter within 2 h of TGF-β addition, consistent with the time-dependent up-regulation of uPAR expression. The primary components present in the TGF-β-stimulated AP-1 complex bound to the uPAR promoter were Jun D and Fra-2. Moreover, addition of SP600125, or expression of DN MKK4 or DN TβRII, blocked TGF-β up-regulation of uPAR in IECs. Accordingly, our results indicate that TGF-β activates the Ras/MKK4/JNK1 signaling cascade, leading to induction of AP-1 activity, which, in turn, up-regulates uPAR expression. Our results also indicate that the type II TGF-β receptor (RII) is required for TGF-β activation of JNK1 and the resulting up-regulation of uPAR expression. © 2003 Wiley-Liss, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/171732
ISSN
2015 Impact Factor: 4.155
2015 SCImago Journal Rankings: 1.842
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorYue, Jen_US
dc.contributor.authorSun, Ben_US
dc.contributor.authorLiu, Gen_US
dc.contributor.authorMulder, KMen_US
dc.date.accessioned2012-10-30T06:16:40Z-
dc.date.available2012-10-30T06:16:40Z-
dc.date.issued2004en_US
dc.identifier.citationJournal Of Cellular Physiology, 2004, v. 199 n. 2, p. 284-292en_US
dc.identifier.issn0021-9541en_US
dc.identifier.urihttp://hdl.handle.net/10722/171732-
dc.description.abstractWe have previously demonstrated that activation of the Ras/Mapk pathways is required for transforming growth factor β (TGF-β) induction of TGF-β 1 expression. Here we examined the role of the Ras/Mapk pathways in TGF-β induction of urokinase-type plasminogen activator receptor (uPAR) expression in untransformed intestinal epithelial cells (IECs). TGF-β activated the stress-activated protein kinases (Sapk)/c-Jun N-terminal kinases (JNKs) within 5-10 min, an effect that preceeded TGF-β induction of uPAR expression in these cells. TGF-β induction of both JNK1 activity and JunD phosphorylation was blocked by expression of a dominant-negative mutant of the type II TGF-β receptor (DN TβRII), a dominant-negative mutant of MKK4 (DN MKK4), or a dominant-negative mutant of Ras (RasN17), or by the addition of the JNK inhibitor SP600125. TGF-β also induced AP-1 complex formation at the distal AP-1 site (-184 to -178) of the uPAR promoter within 2 h of TGF-β addition, consistent with the time-dependent up-regulation of uPAR expression. The primary components present in the TGF-β-stimulated AP-1 complex bound to the uPAR promoter were Jun D and Fra-2. Moreover, addition of SP600125, or expression of DN MKK4 or DN TβRII, blocked TGF-β up-regulation of uPAR in IECs. Accordingly, our results indicate that TGF-β activates the Ras/MKK4/JNK1 signaling cascade, leading to induction of AP-1 activity, which, in turn, up-regulates uPAR expression. Our results also indicate that the type II TGF-β receptor (RII) is required for TGF-β activation of JNK1 and the resulting up-regulation of uPAR expression. © 2003 Wiley-Liss, Inc.en_US
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/31010en_US
dc.relation.ispartofJournal of Cellular Physiologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshElectrophoretic Mobility Shift Assayen_US
dc.subject.meshEnzyme Activation - Drug Effects - Physiologyen_US
dc.subject.meshEnzyme Inhibitors - Pharmacologyen_US
dc.subject.meshEpithelial Cells - Drug Effects - Metabolismen_US
dc.subject.meshHumansen_US
dc.subject.meshImmunoblottingen_US
dc.subject.meshJnk Mitogen-Activated Protein Kinasesen_US
dc.subject.meshMap Kinase Kinase 4en_US
dc.subject.meshMitogen-Activated Protein Kinase Kinases - Drug Effects - Metabolismen_US
dc.subject.meshReceptors, Cell Surface - Drug Effects - Metabolismen_US
dc.subject.meshReceptors, Transforming Growth Factor Beta - Drug Effects - Metabolismen_US
dc.subject.meshReceptors, Urokinase Plasminogen Activatoren_US
dc.subject.meshSignal Transduction - Drug Effects - Physiologyen_US
dc.subject.meshTime Factorsen_US
dc.subject.meshTranscription Factor Ap-1 - Drug Effects - Metabolismen_US
dc.subject.meshTransfectionen_US
dc.subject.meshTransforming Growth Factor Beta - Metabolismen_US
dc.subject.meshUp-Regulationen_US
dc.titleRequirement of TGF-β Receptor-Dependent Activation of c-Jun N-Terminal Kinases (JNKs)/Stress-Activated Protein Kinases (Sapks) for TGF-β Up-Regulation of the Urokinase-Type Plasminogen Activator Receptoren_US
dc.typeArticleen_US
dc.identifier.emailYue, J:jyue@hku.hken_US
dc.identifier.authorityYue, J=rp00286en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1002/jcp.10469en_US
dc.identifier.pmid15040011-
dc.identifier.scopuseid_2-s2.0-1842421169en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-1842421169&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume199en_US
dc.identifier.issue2en_US
dc.identifier.spage284en_US
dc.identifier.epage292en_US
dc.identifier.isiWOS:000220577400014-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridYue, J=7101875828en_US
dc.identifier.scopusauthoridSun, B=8322138300en_US
dc.identifier.scopusauthoridLiu, G=24329989800en_US
dc.identifier.scopusauthoridMulder, KM=7005187184en_US
dc.identifier.citeulike1665147-

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