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CD105 inhibits transforming growth factor-beta-Smad3 signalling
- Source :
- Anticancer research. 24(3a)
- Publication Year :
- 2004
-
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.
- Subjects :
- Transcriptional Activation
Muscle Cells
Blotting, Western
Active Transport, Cell Nucleus
Endoglin
Vascular Cell Adhesion Molecule-1
Receptors, Cell Surface
Transfection
Rats
DNA-Binding Proteins
Transforming Growth Factor beta1
Antigens, CD
Transforming Growth Factor beta
Trans-Activators
Animals
Humans
Mitogen-Activated Protein Kinase 8
Smad3 Protein
Mitogen-Activated Protein Kinases
Phosphorylation
Signal Transduction
Subjects
Details
- ISSN :
- 02507005
- Volume :
- 24
- Issue :
- 3a
- Database :
- OpenAIRE
- Journal :
- Anticancer research
- Accession number :
- edsair.pmid..........72b2c81b6cd09a6512014f05c335ede3