CD105 inhibits transforming growth factor-beta-Smad3 signalling.
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.
Guo
Baoqiang
B
Laboratory Medicine Academic Group, Medical School, University of Manchester, Manchester, UK. Mqbssbg5@fs1.scg.man.ac.uk
Slevin
Mark
M
Li
Chenggang
C
Parameshwar
Sudeep
S
Liu
Donghui
D
Kumar
Pat
P
Bernabeu
Carmelo
C
Kumar
Shant
S
D021581:Active Transport, Cell Nucleus; D000818:Animals; D015703:Antigens, CD; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D000071063:Endoglin; D006801:Humans; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D032342:Muscle Cells / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation; D051381:Rats; D011956:Receptors, Cell Surface; D015398:Signal Transduction / Q000502:physiology; D051900:Smad3 Protein; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D015533:Transcriptional Activation / Q000502:physiology; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000502:physiology; D053773:Transforming Growth Factor beta1; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D015703:Antigens, CD; D004268:DNA-Binding Proteins; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; C497790:SMAD3 protein, human; D051900:Smad3 Protein; C497787:Smad3 protein, rat; C508960:TGFB1 protein, human; C508962:Tgfb1 protein, rat; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D019010:Vascular Cell Adhesion Molecule-1; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases