Endoglin, a TGF-β binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1
Kimberly A. McAllister,Grogg Km,Darren W. Johnson,Carol J. Gallione,Melanie A. Baldwin,Charles E. Jackson,Charles E. Jackson,E A Helmbold,Dorene S. Markel,Wendy McKinnon,Jill R. Murrell +10 more
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Endoglin is identified as the HHT gene mapping to 9q3 and HHT is established as the first human disease defined by a mutation in a member of the TGF-β receptor complex.Abstract:
Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by multisystemic vascular dysplasia and recurrent haemorrhage. Linkage for some families has been established to chromosome 9q33−q34. In the present study, endoglin, a transforming growth factor beta (TGF-beta) binding protein, was analysed as a candidate gene for the disorder based on chromosomal location, expression pattern and function. We have identified mutations in three affected individuals: a C to G substitution converting a tyrosine to a termination codon, a 39 base pair deletion and a 2 base pair deletion which creates a premature termination codon. We have identified endoglin as the HHT gene mapping to 9q3 and have established HHT as the first human disease defined by a mutation in a member of the TGF-beta receptor complex.read more
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References
More filters
Journal ArticleDOI
Targeted disruption of the mouse transforming growth factor-β1 gene results in multifocal inflammatory disease
Marcia M. Shull,Ilona Ormsby,Ann B. Kier,Sharon A. Pawlowski,Ronald J. Diebold,Moying Yin,Ruth D. Allen,Charles L. Sidman,Gabriele Proetzel,Dawn Calvin,Nikki Annunziata,Thomas Doetschman +11 more
TL;DR: TGF-β1-deficient mice may be valuable models for human immune and inflammatory disorders, including autoimmune diseases, transplant rejection and graft versus host reactions.
Journal ArticleDOI
Mechanism of activation of the TGF-β receptor
TL;DR: The role of TGF-β binds directly to receptor II, which is a constitutively active kinase, and phosphorylation allows receptor I to propagate the signal to downstream substrates, providing a mechanism by which a cytokine can generate the first step of a signalling cascade.
Journal ArticleDOI
Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death.
Ashok B. Kulkarni,Chang-Goo Huh,Dean Becker,Andrew G. Geiser,Marion Lyght,Kathleen C. Flanders,Anita B. Roberts,Michael B. Sporn,Jerrold M. Ward,Stefan Karlsson +9 more
TL;DR: Pathological examination revealed an excessive inflammatory response with massive infiltration of lymphocytes and macrophages in many organs, but primarily in heart and lungs, which suggests a prominent role for TGF-beta 1 in homeostatic regulation of immune cell proliferation and extravasation into tissues.
Journal ArticleDOI
TGFβ signals through a heteromeric protein kinase receptor complex
Jeffrey L. Wrana,Liliana Attisano,Juan M. Cárcamo,A Zentella,Jacqueline Doody,Marikki Laiho,Xiao-Fan Wang,Joan Massagué +7 more
TL;DR: It is shown that the type II receptor requires both its kinase activity and association with another TGF beta-binding protein, the type I receptor, to signal growth inhibition and early gene responses.
Journal ArticleDOI
Betaglycan presents ligand to the TGFβ signaling receptor
TL;DR: Transforming growth factor β signals through a heteromeric protein kinase receptor that has a limited ability to bind ligand is overcome by the action of betaglycan (TGFβ type III receptor), a separate TGFβ-binding membrane protein of previously unknown function.