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 conserved among flies, frogs, and mammals (reviewed in Refs. 1-4). These factors control biological processes such as embryogenesis, organogenesis, morphogenesis of tissues like bone and cartilage, vasculogenesis, wound repair and angiogenesis, hematopoiesis, and immune regulation (reviewed in Refs. 2 and 4 -8). Signaling by ligands of the TGF- superfamily is mediated by a high affinity, ligand-induced, heteromeric complex consisting of related Ser/Thr kinase receptors divided into two subfamilies, type I and type II (3). Formation of this high affinity complex is essential, as the type II receptor transphosphorylates and activates the type I receptor in a Gly/Ser-rich region (9 -11). The type I receptor in turn phosphorylates and transduces signals to a novel family of recently identified downstream targets, termed Smads (12, 13).Although the cooperativity between two kinase receptors is a general signaling mechanism for the TGF- superfamily, where the type I receptors are considered the signal transducing receptors, ligand binding ability is not restricted to receptor type. For TGF- and activin, the type II receptors TRII and ActRII or ActRIIB, respectively, are known to bind ligand independently (14 -16), while the corresponding type I receptors ALK5 (activin receptor-like kinase; TRI) or ALK4 (ActRIB) require the coexpression of the appropriate type II receptors (9,(17)(18)(19)(20)(21). The BMP family differs in this respect as the BMP type I receptors, ALK3 (BMPRI) and ALK6 (BMPRIB), can bind BMP-2 and B...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.