Endoglin forms a heteromeric complex with the signaling receptors for transforming growth factor-beta

• Published in: The Journal of biological chemistry 1994-01, Vol.269 (3), p.1995-2001
• Main Authors: YAMASHITA, H, ICHIJO, H, GRIMSBY, S, MOREN, A, TEN DIJKE, P, MIYAZONO, K
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Analytical, structural and metabolic biochemistry; Animals; Antigens, CD; Aorta; Base Sequence; Biological and medical sciences; Cloning, Molecular; DNA, Complementary - metabolism; Endoglin; Endothelium, Vascular - metabolism; Female; Fundamental and applied biological sciences. Psychology; Gene Library; Humans; Macromolecular Substances; Membrane Glycoproteins - biosynthesis; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Miscellaneous; Molecular Sequence Data; Phosphorylation; Protein Biosynthesis; Proteins; Receptors, Cell Surface; Receptors, Transforming Growth Factor beta - metabolism; Recombinant Proteins - metabolism; Recombinant Proteins - pharmacology; Sequence Homology, Amino Acid; Signal Transduction; Swine; Transforming Growth Factor beta - metabolism; Transforming Growth Factor beta - pharmacology; Uterus - metabolism; Vascular Cell Adhesion Molecule-1
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(17)42126-0

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.