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- Publisher Website: 10.1002/jcp.10469
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- PMID: 15040011
- WOS: WOS:000220577400014
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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
Title | 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 |
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Authors | |
Issue Date | 2004 |
Publisher | John 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? |
Abstract | We 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 Identifier | http://hdl.handle.net/10722/171732 |
ISSN | 2021 Impact Factor: 6.513 2020 SCImago Journal Rankings: 1.529 |
ISI Accession Number ID | |
References |
DC Field | Value | Language |
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dc.contributor.author | Yue, J | en_US |
dc.contributor.author | Sun, B | en_US |
dc.contributor.author | Liu, G | en_US |
dc.contributor.author | Mulder, KM | en_US |
dc.date.accessioned | 2012-10-30T06:16:40Z | - |
dc.date.available | 2012-10-30T06:16:40Z | - |
dc.date.issued | 2004 | en_US |
dc.identifier.citation | Journal Of Cellular Physiology, 2004, v. 199 n. 2, p. 284-292 | en_US |
dc.identifier.issn | 0021-9541 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/171732 | - |
dc.description.abstract | We 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.language | eng | en_US |
dc.publisher | John Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/31010 | en_US |
dc.relation.ispartof | Journal of Cellular Physiology | en_US |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Cells, Cultured | en_US |
dc.subject.mesh | Electrophoretic Mobility Shift Assay | en_US |
dc.subject.mesh | Enzyme Activation - Drug Effects - Physiology | en_US |
dc.subject.mesh | Enzyme Inhibitors - Pharmacology | en_US |
dc.subject.mesh | Epithelial Cells - Drug Effects - Metabolism | en_US |
dc.subject.mesh | Humans | en_US |
dc.subject.mesh | Immunoblotting | en_US |
dc.subject.mesh | Jnk Mitogen-Activated Protein Kinases | en_US |
dc.subject.mesh | Map Kinase Kinase 4 | en_US |
dc.subject.mesh | Mitogen-Activated Protein Kinase Kinases - Drug Effects - Metabolism | en_US |
dc.subject.mesh | Receptors, Cell Surface - Drug Effects - Metabolism | en_US |
dc.subject.mesh | Receptors, Transforming Growth Factor Beta - Drug Effects - Metabolism | en_US |
dc.subject.mesh | Receptors, Urokinase Plasminogen Activator | en_US |
dc.subject.mesh | Signal Transduction - Drug Effects - Physiology | en_US |
dc.subject.mesh | Time Factors | en_US |
dc.subject.mesh | Transcription Factor Ap-1 - Drug Effects - Metabolism | en_US |
dc.subject.mesh | Transfection | en_US |
dc.subject.mesh | Transforming Growth Factor Beta - Metabolism | en_US |
dc.subject.mesh | Up-Regulation | en_US |
dc.title | 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 | en_US |
dc.type | Article | en_US |
dc.identifier.email | Yue, J:jyue@hku.hk | en_US |
dc.identifier.authority | Yue, J=rp00286 | en_US |
dc.description.nature | link_to_subscribed_fulltext | en_US |
dc.identifier.doi | 10.1002/jcp.10469 | en_US |
dc.identifier.pmid | 15040011 | - |
dc.identifier.scopus | eid_2-s2.0-1842421169 | en_US |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-1842421169&selection=ref&src=s&origin=recordpage | en_US |
dc.identifier.volume | 199 | en_US |
dc.identifier.issue | 2 | en_US |
dc.identifier.spage | 284 | en_US |
dc.identifier.epage | 292 | en_US |
dc.identifier.isi | WOS:000220577400014 | - |
dc.publisher.place | United States | en_US |
dc.identifier.scopusauthorid | Yue, J=7101875828 | en_US |
dc.identifier.scopusauthorid | Sun, B=8322138300 | en_US |
dc.identifier.scopusauthorid | Liu, G=24329989800 | en_US |
dc.identifier.scopusauthorid | Mulder, KM=7005187184 | en_US |
dc.identifier.citeulike | 1665147 | - |
dc.identifier.issnl | 0021-9541 | - |