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.
MeSH terms
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Active Transport, Cell Nucleus
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Animals
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Antigens, CD
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Blotting, Western
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DNA-Binding Proteins / antagonists & inhibitors*
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DNA-Binding Proteins / metabolism
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DNA-Binding Proteins / physiology
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Endoglin
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Humans
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Mitogen-Activated Protein Kinase 8
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Mitogen-Activated Protein Kinases / metabolism
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Muscle Cells / metabolism
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Muscle Cells / physiology
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Phosphorylation
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Rats
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Receptors, Cell Surface
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Signal Transduction / physiology
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Smad3 Protein
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Trans-Activators / antagonists & inhibitors*
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Trans-Activators / metabolism
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Trans-Activators / physiology
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Transcriptional Activation / physiology
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Transfection
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Transforming Growth Factor beta / antagonists & inhibitors*
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Transforming Growth Factor beta / physiology
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Transforming Growth Factor beta1
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Vascular Cell Adhesion Molecule-1 / biosynthesis
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Vascular Cell Adhesion Molecule-1 / genetics
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Vascular Cell Adhesion Molecule-1 / physiology*
Substances
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Antigens, CD
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DNA-Binding Proteins
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ENG protein, human
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Endoglin
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Receptors, Cell Surface
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SMAD3 protein, human
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Smad3 Protein
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Smad3 protein, rat
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TGFB1 protein, human
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Tgfb1 protein, rat
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Trans-Activators
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Transforming Growth Factor beta
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Transforming Growth Factor beta1
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Vascular Cell Adhesion Molecule-1
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Mitogen-Activated Protein Kinase 8
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Mitogen-Activated Protein Kinases