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CD105 inhibits transforming growth factor-beta-Smad3 signalling

AuthorsGuo, Baoqiang; Slevin, Mark; Li, Chenggang; Parameshwar, Sudeep; Liu, Donghui; Kumar, Pat; Bernabéu, Carmelo ; Kumar, Shant
Issue DateMay-2004
PublisherInternational Institute of Anticancer Research
CitationAnticancer Research, 24 (3A) : 1337-1345 (2004)
AbstractCD105 (endoglin) is an important component of the transforming growth factor-‚ (TGF-‚) 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- ‚1 signalling, in this preliminary communication, CD105 transfected rat myoblasts were utilized as an in vitro model. Overexpression of CD105 in these ransfectants antagonised TGF-‚1-mediated inhibition of cell proliferation and reduced TGF-‚1- mediated p3TP-Lux (PAI-1 promoter) luciferase activity. It also reduced (CAGA)12-Luc luciferase activity in response to TGF-‚1. The CAGA sequence is specific for Smad3/4 binding, implying that CD105 is involved in inhibition of TGF- ‚1/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. The transforming growth factor-‚ (TGF-‚) super family plays a critical role in a wide range of biological processes including tumorigenesis (1). TGF-‚s exert their function through binding to their specific receptors, such as type I (T‚RI) and type II (T‚RII), betaglycan and CD105 (endoglin) (2,3). TGF-‚ binding to the constitutively phosphorylated T‚RII is followed by recruitment of T‚RI into the complex, phosphorylation of T‚RI and activation of Smad proteins, which in turn transmit signals into the nucleus (4,5)
Description9 páginas, 4 figuras -- PAGS nros. 1337-1345
Appears in Collections:(CIB) Artículos
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