Endoglin Is an Accessory Protein That Interacts with the Signaling Receptor Complex of Multiple Members of the Transforming Growth Factor- Superfamily
ABSTRACT Endoglin (CD105) is a transmembrane glycoprotein that binds transforming growth factor (TGF)-β1 and -β3, 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-β1 and -β3, 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-β1 and -β3 by associating with the TGF-β 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-β superfamily.
- SourceAvailable from: Yuko Mori-Akiyama
[Show abstract] [Hide abstract]
- "A number of signaling pathways control either the expression or the activity of SOX9 in chondrocytes. Bmp signaling is needed for formation of chondrogenic mesenchymal condensations and for expression or maintenance of Sox9 RNA at this step . Interleukin-1 and tumor necrosis factor alpha inhibit Sox9 expression, whereas fibroblast growth factor (FGF) upregulates Sox9 through mitogen-activated protein kinase signaling. "
ABSTRACT: The transcription factor SOX9 plays an essential role in determining the fate of several cell types and is a master factor in regulation of chondrocyte development. Our aim was to determine which genes in the genome of chondrocytes are either directly or indirectly controlled by SOX9. We used RNA-Seq to identify genes whose expression levels were affected by SOX9 and used SOX9 ChIP-Seq to identify those genes that harbor SOX9-interaction sites. For RNA-Seq, the RNA expression profile of primary Sox9flox/flox mouse chondrocytes infected with Ad-CMV-Cre was compared with that of the same cells infected with a control adenovirus. Analysis of RNA-Seq data indicated that, when the levels of Sox9 mRNA were decreased more than 8-fold by infection with Ad-CMV-Cre, 196 genes showed a decrease in expression of at least 4-fold. These included many cartilage extracellular matrix (ECM) genes and a number of genes for ECM modification enzymes (transferases), membrane receptors, transporters, and others. In ChIP-Seq, 75% of the SOX9-interaction sites had a canonical inverted repeat motif within 100 bp of the top of the peak. SOX9-interaction sites were found in 55% of the genes whose expression was decreased more than 8-fold in SOX9-depleted cells and in somewhat fewer of the genes whose expression was reduced more than 4-fold, suggesting that these are direct targets of SOX9. The combination of RNA-Seq and ChIP-Seq has provided a fuller understanding of the SOX9-controlled genetic program of chondrocytes.PLoS ONE 09/2014; 9(9):e107577. DOI:10.1371/journal.pone.0107577 · 3.23 Impact Factor
[Show abstract] [Hide abstract]
- "Mouse MSCs are similar to their human counterparts, except that they can lack or be heterogeneous for both CD73 and CD90  . CD105/endoglin is a high affinity coreceptor for transforming growth factor (TGF)-í µí»½1 and TGF-í µí»½3 . Although CD105 is generally considered to be an important MSC marker  , several reports have shown that its expression varies depending upon the source of MSCs (bone marrow, adipose tissue, umbilical cord blood, or placenta), the culture time in vitro, and differentiation status    . "
ABSTRACT: Adipose tissue-derived stromal cells, termed ASCs, play an important role in regenerative applications. They resemble mesenchymal stem cells owing to their inexhaustibility, general differentiation potential, and plasticity and display a series of cell-specific and cluster-of-differentiation (CD) marker profiles similar to those of other somatic stem cells. Variations in phenotypes or differentiation are intimately associated with CD markers. The purpose of our study was to exhibit distinct populations of ASCs with differing characteristics for osteogenic differentiation. The primary cell batch of murine-derived ASCs was extracted from subcutaneous adipose tissue and the cells were sorted for the expression of the surface protein molecules CD90 and CD105 using flow cytometry. Each cell population sorted for CD90 and CD105 was analyzed for osteogenic potency after cell culture. The results suggested that ASCs exhibit distinct populations with differing characteristics for osteogenic differentiation: unsorted ASCs stimulated comparable mineralized nodule formation as bone marrow stromal cells (BMSCs) in osteogenic medium and viral transfection for BMP2 accelerated the formation of mineralized nodules in CD90 and/or CD105 positive ASCs with observation of decrease in CD105 expression after 14 days. Future studies assessing different immunophenotypes of ASCs should be undertaken to develop cell-based tissue engineering.Stem cell International 09/2014; DOI:10.1155/2014/576358 · 2.81 Impact Factor
- "Endoglin is a type I transmembrane glycoprotein primarily expressed by vascular endothelial cells . Functionally, endoglin modulates TGF-í µí»½ superfamily signaling pathways through interaction with ligand-binding receptors or direct binding of ligands   . Most notably, mutations in the endoglin (ENG) gene lead to the autosomal dominant vascular disorder, hereditary hemorrhagic telangiectasia type 1 (HHT1) . "
Dataset: 2014 MI MAK