Linked Life Data

18925455

Source:http://linkedlifedata.com/resource/pubmed/id/18925455

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-10-17
pubmed:abstractText
The serine protease tissue-type plasminogen activator (tPA), a key enzyme in hemostasis, is activated by protein aggregates with amyloid-like properties. tPA is implicated in various pathologies, including amyloidoses. A major task is to further elucidate the mechanisms of amyloid pathology. We here show that the fibronectin type I domain of tPA mediates the interaction with amyloid protein aggregates. We found that in contrast to full-length tPA, a deletion-mutant of tPA, lacking the first three N-terminal domains (including the fibronectin type I domain), fails to activate in response to amyloid protein aggregates. Using recombinantly produced domains of tPA in direct binding assays, we subsequently mapped the amyloid-binding region to the fibronectin type I domain. This domain co-localized with congophilic plaques in brain sections from patients with Alzheimer's disease. Fibronectin type I domains from homologous proteases factor XII, hepatocyte growth factor activator and from the extracellular matrix protein fibronectin also bound to aggregated amyloidogenic peptides. Finally, we demonstrated that the isolated fibronectin type I domain inhibits amyloid-induced aggregation of blood platelets. The identification of the fibronectin type I domain as an amyloid-binding module provides new insights into the (patho-) physiological role of tPA and the homologous proteins which may offer new targets for intervention in amyloid pathology.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1744-2818
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
166-80
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Identification of fibronectin type I domains as amyloid-binding modules on tissue-type plasminogen activator and three homologs.
pubmed:affiliation
Department of Clinical Chemistry and Haematology, University Medical Center Utrecht and Institute for Biomembranes, P O Box 85500, Utrecht, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't