TY - JOUR T1 - CD105 Inhibits Transforming Growth Factor-ß-Smad3 Signalling JF - Anticancer Research JO - Anticancer Res SP - 1337 LP - 1346 VL - 24 IS - 3A AU - BAOQIANG GUO AU - MARK SLEVIN AU - CHENGGANG LI AU - SUDEEP PARAMESHWAR AU - DONGHUI LIU AU - PAT KUMAR AU - CARMELO BERNABEU AU - SHANT KUMAR Y1 - 2004/05/01 UR - http://ar.iiarjournals.org/content/24/3A/1337.abstract N2 - CD105 (endoglin) is an important component of the transforming growth factor-β (TGF-β) 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- β1 signalling, in this preliminary communication, CD105 transfected rat myoblasts were utilized as an in vitro model. Overexpression of CD105 in these transfectants antagonised TGF-β1-mediated inhibition of cell proliferation and reduced TGF-β1-mediated p3TP-Lux (PAI-1 promoter) luciferase activity. It also reduced (CAGA)12-Luc luciferase activity in response to TGF-β1. The CAGA sequence is specific for Smad3/4 binding, implying that CD105 is involved in inhibition of TGF- β1/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. Copyright© 2004 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved ER -