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.
Laboratory Medicine Academic Group, Medical School, University of Manchester, Manchester, UK. Mqbssbg5@fs1.scg.man.ac.uk
Baoqiang
B
Guo
Mark
M
Slevin
Chenggang
C
Li
Sudeep
S
Parameshwar
Donghui
D
Liu
Pat
P
Kumar
Carmelo
C
Bernabeu
Shant
S
Kumar
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