Linked Life Data

16282348

Source:http://linkedlifedata.com/resource/pubmed/id/16282348

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2006-2-22
pubmed:abstractText
Genetic studies in mouse and zebrafish have established the importance of activin receptor-like kinase 1 (ALK1) in formation and remodeling of blood vessels. Single-allele mutations in the ALK1 gene have been linked to the human type 2 hereditary hemorrhagic telangiectasia (HHT2). However, how these ALK1 mutations contribute to this disorder remains unclear. To explore the mechanism underlying effect of the HHT-related ALK1 mutations on receptor activity, we generated 11 such mutants and investigated their signaling activities using reporter assay in mammalian cells and examined their effect on zebrafish embryogenesis. Here we show that some of the HHT2-related mutations generate a dominant-negative effect whereas the others give rise to a null phenotype via loss of protein expression or receptor activity. These data indicate that loss-of-function mutations in a single allele of the ALK1 locus are sufficient to contribute to defects in maintaining endothelial integrity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
107
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1951-4
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Functional analysis of mutations in the kinase domain of the TGF-beta receptor ALK1 reveals different mechanisms for induction of hereditary hemorrhagic telangiectasia.
pubmed:affiliation
State Key Laboratory of Biomembrane and Membrane Biotechnology, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't