Linked Life Data

10767348

Source:http://linkedlifedata.com/resource/pubmed/id/10767348

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2000-6-23
pubmed:abstractText
ALK-1 (activin receptor-like kinase-1), a type I receptor of the transforming growth factor (TGF)-beta superfamily, is the gene mutated in hereditary hemorrhagic telangiectasia type 2 (HHT2) while endoglin is mutated in HHT1. Using a novel polyclonal antibody to ALK-1, we measured ALK-1 expression on human umbilical vein endothelial cells (HUVEC) of newborns from HHT families whose affected members had normal endoglin levels. ALK-1 levels were specifically reduced in three HUVEC with ALK-1 missense mutant codons, and normal in two newborns not carrying the missense mutations present in the clinically affected relatives. Levels were also normal in a HUVEC with deletion of S232 in the ATP binding site of ALK-1. Thus HHT2 appears to be associated with a loss of function of the mutant allele due to a reduction in either protein level or activity. We also report three new ALK-1 missense mutations leading to G48E/A49P, C344Y and E407D substitutions. In COS-1 transfected cells, ALK-1 was found in the TGF-beta1 and -beta3 receptor complexes in association with endoglin and TbetaRII, but not in activin receptor complexes containing endoglin. In HUVEC, ALK-1 was not detectable in the TGF-beta1 or -beta3 receptor complexes. However, in the absence of ligand, ALK-1 and endoglin interactions were observed by immunoprecipitation/western blot in HUVEC from normal as well as HHT1 and HHT2 patients. Our data suggest a transient association between these two proteins of the TGF-beta superfamily, both required at a critical level to ensure vessel wall integrity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1227-37
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10767348-Activin Receptors, pubmed-meshheading:10767348-Amino Acid Substitution, pubmed-meshheading:10767348-Antigens, CD, pubmed-meshheading:10767348-Base Sequence, pubmed-meshheading:10767348-Cells, Cultured, pubmed-meshheading:10767348-Endothelium, Vascular, pubmed-meshheading:10767348-Family, pubmed-meshheading:10767348-Female, pubmed-meshheading:10767348-Genomic Imprinting, pubmed-meshheading:10767348-Humans, pubmed-meshheading:10767348-Infant, Newborn, pubmed-meshheading:10767348-Mutation, Missense, pubmed-meshheading:10767348-Placenta, pubmed-meshheading:10767348-Pregnancy, pubmed-meshheading:10767348-Protein-Serine-Threonine Kinases, pubmed-meshheading:10767348-Receptors, Cell Surface, pubmed-meshheading:10767348-Receptors, Transforming Growth Factor beta, pubmed-meshheading:10767348-Sequence Deletion, pubmed-meshheading:10767348-Telangiectasia, Hereditary Hemorrhagic, pubmed-meshheading:10767348-Umbilical Veins, pubmed-meshheading:10767348-Vascular Cell Adhesion Molecule-1
pubmed:year
2000
pubmed:articleTitle
Analysis of ALK-1 and endoglin in newborns from families with hereditary hemorrhagic telangiectasia type 2.
pubmed:affiliation
Cancer and Blood Research Programme, The Hospital for Sick Children, and Department of Immunology, University of Toronto, Toronto M5G 1X8, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't