title: Endoglin forms a heteromeric complex with the signaling receptors for transforming growth factor-beta.
abstract: Human endoglin is a dimeric protein that binds transforming growth factor-beta (TGF-beta). A porcine cDNA clone for endoglin was obtained from a porcine uterus cDNA library. The deduced sequence of the primary translated product of endoglin consists of 643 amino acids with a high sequence identity (96%) to human endoglin in the transmembrane and intracellular domains, but with a lower sequence similarity (66%) in the extracellular domain. In contrast to human endoglin, porcine endoglin has no Arg-Gly-Asp tripeptide in its sequence. Antibodies, raised against a peptide corresponding to the intracellular domain of porcine endoglin, immunoprecipitated an 84-kDa protein under reducing condition and a 130-kDa protein under nonreducing condition in porcine aortic endothelial cells. Porcine endoglin bound TGF-beta 1 and -beta 3 efficiently, but TGF-beta 2 less efficiently. Endoglin was found to be coimmunoprecipitated with TGF-beta receptors type I and/or II by the endoglin antibodies or by TGF-beta receptor II antibodies in the presence of ligand. Thus, endoglin and TGF-beta receptors I and/or II most likely formed a heteromeric receptor complex. Endoglin was phosphorylated on serine residue(s), which did not change after stimulation by TGF-beta 1. These results revealed that endoglin is a phosphorylated protein which forms a heteromeric complex with signaling receptors for TGF-beta.
authors.affiliation: Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Yamashita
authors.forename: H
authors.initials: H
authors.lastname: Ichijo
authors.forename: S
authors.initials: S
authors.lastname: Grimsby
authors.forename: A
authors.initials: A
authors.lastname: Morén
authors.forename: P
authors.initials: P
authors.lastname: ten Dijke
authors.forename: K
authors.initials: K
authors.lastname: Miyazono
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D001011:Aorta; D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D000071063:Endoglin; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D015723:Gene Library; D006801:Humans; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D014176:Protein Biosynthesis; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013552:Swine; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology; D014599:Uterus / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1
chemical_list: D015703:Antigens, CD; D018076:DNA, Complementary; C064206:ENG protein, human; D000071063:Endoglin; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D019010:Vascular Cell Adhesion Molecule-1