2.50
Hdl Handle:
http://hdl.handle.net/10541/77734
Title:
CD105 inhibits transforming growth factor-beta-Smad3 signalling.
Authors:
Guo, Baoqiang; Slevin, Mark; Li, Chenggang; Parameshwar, Sudeep; Liu, Donghui; Kumar, Patricia; Bernabeu, Carmelo; Kumar, Shant
Abstract:
CD105 (endoglin) is an important component of the transforming growth factor-beta (TGF-beta) receptor complex and is highly expressed in endothelial cells in tissues undergoing angiogenesis such as healing wounds, infarcts and in a wide range of tumours. In an attempt to understand the molecular mechanism by which CD105 exerts its effects on angiogenesis by modulating TGF-beta1 signalling, in this preliminary communication, CD105 transfected rat myoblasts were utilized as an in vitro model. Overexpression of CD105 in these transfectants antagonised TGF-beta1-mediated inhibition of cell proliferation and reduced TGF-beta1-mediated p3TP-Lux (PAI-1 promoter) luciferase activity. It also reduced (CAGA)12-Luc luciferase activity in response to TGF-beta1. The CAGA sequence is specific for Smad3/4 binding, implying that CD105 is involved in inhibition of TGF-beta1/Smad3 signalling. Furthermore, CD105 overexpression reduced serine phosphorylation of Smad3 and inhibited subsequent nuclear translocation of Smad3. CD105 resulted in high phosphorylation of JNK1, which is able to activate c-Jun. c-Jun is known to inhibit Smad3 transcriptional activity on CAGA sites, suggesting that CD105 may also inhibit Smad3 signalling through JNK1.
Affiliation:
Laboratory Medicine Academic Group, Medical School, University of Manchester, Manchester, UK. Mqbssbg5@fs1.scg.man.ac.uk
Citation:
CD105 inhibits transforming growth factor-beta-Smad3 signalling., 24 (3a):1337-45 Anticancer Res.
Journal:
Anticancer Research
Issue Date:
2004
URI:
http://hdl.handle.net/10541/77734
PubMed ID:
15274293
Type:
Article
Language:
en
ISSN:
0250-7005
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorGuo, Baoqiang-
dc.contributor.authorSlevin, Mark-
dc.contributor.authorLi, Chenggang-
dc.contributor.authorParameshwar, Sudeep-
dc.contributor.authorLiu, Donghui-
dc.contributor.authorKumar, Patricia-
dc.contributor.authorBernabeu, Carmelo-
dc.contributor.authorKumar, Shant-
dc.date.accessioned2009-08-18T14:37:16Z-
dc.date.available2009-08-18T14:37:16Z-
dc.date.issued2004-
dc.identifier.citationCD105 inhibits transforming growth factor-beta-Smad3 signalling., 24 (3a):1337-45 Anticancer Res.en
dc.identifier.issn0250-7005-
dc.identifier.pmid15274293-
dc.identifier.urihttp://hdl.handle.net/10541/77734-
dc.description.abstractCD105 (endoglin) is an important component of the transforming growth factor-beta (TGF-beta) receptor complex and is highly expressed in endothelial cells in tissues undergoing angiogenesis such as healing wounds, infarcts and in a wide range of tumours. In an attempt to understand the molecular mechanism by which CD105 exerts its effects on angiogenesis by modulating TGF-beta1 signalling, in this preliminary communication, CD105 transfected rat myoblasts were utilized as an in vitro model. Overexpression of CD105 in these transfectants antagonised TGF-beta1-mediated inhibition of cell proliferation and reduced TGF-beta1-mediated p3TP-Lux (PAI-1 promoter) luciferase activity. It also reduced (CAGA)12-Luc luciferase activity in response to TGF-beta1. The CAGA sequence is specific for Smad3/4 binding, implying that CD105 is involved in inhibition of TGF-beta1/Smad3 signalling. Furthermore, CD105 overexpression reduced serine phosphorylation of Smad3 and inhibited subsequent nuclear translocation of Smad3. CD105 resulted in high phosphorylation of JNK1, which is able to activate c-Jun. c-Jun is known to inhibit Smad3 transcriptional activity on CAGA sites, suggesting that CD105 may also inhibit Smad3 signalling through JNK1.en
dc.language.isoenen
dc.subject.meshActive Transport, Cell Nucleus-
dc.subject.meshAnimals-
dc.subject.meshAntigens, CD-
dc.subject.meshBlotting, Western-
dc.subject.meshDNA-Binding Proteins-
dc.subject.meshHumans-
dc.subject.meshMitogen-Activated Protein Kinase 8-
dc.subject.meshMitogen-Activated Protein Kinases-
dc.subject.meshMuscle Cells-
dc.subject.meshPhosphorylation-
dc.subject.meshRats-
dc.subject.meshReceptors, Cell Surface-
dc.subject.meshSignal Transduction-
dc.subject.meshSmad3 Protein-
dc.subject.meshTrans-Activators-
dc.subject.meshTranscriptional Activation-
dc.subject.meshTransfection-
dc.subject.meshTransforming Growth Factor beta-
dc.subject.meshTransforming Growth Factor beta1-
dc.subject.meshVascular Cell Adhesion Molecule-1-
dc.titleCD105 inhibits transforming growth factor-beta-Smad3 signalling.en
dc.typeArticleen
dc.contributor.departmentLaboratory Medicine Academic Group, Medical School, University of Manchester, Manchester, UK. Mqbssbg5@fs1.scg.man.ac.uken
dc.identifier.journalAnticancer Researchen

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