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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.
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
html.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.


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