Abstract: |
Endoglin, a dimeric membrane glycoprotein expressed at high levels on human vascular endothelial cells, shares regions of sequence identity with betaglycan, a major binding protein for transforming growth factor-β (TGF- β) that co-exists with TGF-β receptors I and II in a variety of cell lines but is low or absent in endothelial cells. We have examined whether endoglin also binds TGF-β and demonstrate here that the major TGF-β1-binding protein co-existing with TGF-β receptors I and II on human umbilical vein endothelial cells is endoglin, as determined by specific immunoprecipitation of endoglin affinity-labeled with 125I-TGF-β. Furthermore, endoglin ectopically expressed in COS cells binds TGF-β1. Competition affinity- labeling experiments showed that endoglin binds TGF-β1 (K(D) ~ 50 pM) and TGF-β3 with high affinity but fails to bind TGF-β2. This difference in affinity of endoglin for the TGF-β isoforms is in contrast to betaglycan which recognizes all three isoforms. TGF-β however is binding with high affinity to only a small fraction of the available endoglin molecules, suggesting that some rate-limiting event is required to sustain TGF-β binding to endoglin. |
Keywords: |
unclassified drug; human cell; binding affinity; cells, cultured; gene expression; transforming growth factor beta; gene product; transfection; endothelium cell; amino acid sequence; endothelium, vascular; membrane glycoproteins; membrane protein; endoglin; receptors, transforming growth factor beta; protein structure; sequence homology; molecular weight; receptor binding; in vitro; receptors, cell surface; precipitin tests; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; macromolecular systems; betaglycan
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