Endoglin Is an Accessory Protein That Interacts with the Signaling Receptor Complex of Multiple Members of the Transforming Growth Factor-beta Superfamily (original) (raw)

1999, Journal of Biological Chemistry

Endoglin (CD105) is a transmembrane glycoprotein that binds transforming growth factor (TGF)-␤1 and-␤3, 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-␤1 and-␤3, 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-␤1 and-␤3 by associating with the TGF-␤ 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-␤ superfamily. The TGF-␤ 1 superfamily of structurally related peptides includes the TGF-␤ isoforms, ␤1, ␤2, ␤3, and ␤5, the activins and the bone morphogenetic proteins (BMPs). TGF-␤-like factors are a multifunctional set of growth and differentiation factors