Endoglin is an accessory protein that interacts with the signaling receptor complex of multiple members of the transforming growth factor-beta superfamily.
Endoglin (CD105) is a transmembrane glycoprotein that binds transforming growth factor (TGF)-beta1 and -beta3, and coprecipitates with the Ser/Thr kinase signaling receptor complex by affinity labeling of endothelial and leukemic cells. The present study shows that in addition to TGF-beta1 and -beta3, endoglin interacts with activin-A, bone morphogenetic protein (BMP)-7, and BMP-2 but requires coexpression of the respective ligand binding kinase receptor for this association. Endoglin cannot bind ligands on its own and does not alter binding to the kinase receptors. It binds TGF-beta1 and -beta3 by associating with the TGF-beta type II receptor and interacts with activin-A and BMP-7 via activin type II receptors, ActRII and ActRIIB, regardless of which type I receptor partner is coexpressed. However, endoglin binds BMP-2 by interacting with the ligand binding type I receptors, ALK3 and ALK6. The formation of heteromeric signaling complexes was not altered by the presence of endoglin, although it was coprecipitated with these complexes. Endoglin did not interact with BMP-7 through complexes containing the BMP type II receptor, demonstrating specificity of its action. Our data suggest that endoglin is an accessory protein of multiple kinase receptor complexes of the TGF-beta superfamily.
Barbara
N P
NP
Cancer and Blood Research Program, Toronto M5G 1X8, Ontario, Canada.
Wrana
J L
JL
Letarte
M
M
D028341:Activins; D000818:Animals; D015703:Antigens, CD; D055419:Bone Morphogenetic Protein 7; D052005:Bone Morphogenetic Protein Receptors, Type I; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D019556:COS Cells; D002478:Cells, Cultured; D004072:Digitonin / Q000494:pharmacology; D000071063:Endoglin; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007265:Inhibins / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D015703:Antigens, CD; C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D019010:Vascular Cell Adhesion Molecule-1; D028341:Activins; D007265:Inhibins; D017346:Protein Serine-Threonine Kinases; C498214:BMPR1B protein, human; D052005:Bone Morphogenetic Protein Receptors, Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D004072:Digitonin