Linked Life Data

10514510

Source:http://linkedlifedata.com/resource/pubmed/id/10514510

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
42
pubmed:dateCreated
1999-11-19
pubmed:abstractText
Activity of endothelial Tie2 receptor tyrosine kinase is modulated by two naturally occurring, secreted ligands, angiopoietin-1 and -2, which have opposing effects on its phosphorylation. Receptor tyrosine kinase activation requires receptor dimerization/multimerization, which, for many receptors, is mediated by homo-oligomeric ligands binding to and bridging receptor molecules. We show here that angiopoietin-1 and -2 form distinct arrays of disulfide-linked homo-oligomeric complexes. Their mobilities on nonreducing gels suggest that angiopoietin-2 exists predominantly as a homodimer but also forms higher order multimers. In contrast, angiopoietin-1 forms some homotrimers, but predominantly exists in higher order multimers. These two structurally related, 60% homologous ligands are predominantly composed of an amino-terminal coiled coil domain and a carboxyl-terminal fibrinogen-like domain. We show that their distinct oligomerization patterns are determined by their coiled coil domains and, furthermore, that their coiled coil domains, but not their fibrinogen-like domains, are sufficient to mediate formation of disulfide-linked homo-oligomers. In contrast, the differential effects of these ligands on endothelial Tie2 phosphorylation is mediated by their fibrinogen-like domains. We conclude from these studies that the coiled coil and fibrinogen-like domains of the angiopoietins have distinct functions with the coiled coil domain mediating ligand homo-oligomerization and the fibrinogen-like domain mediating ligand activity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
274
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
30196-201
pubmed:dateRevised
2011-8-3
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Angiopoietin-1 and -2 coiled coil domains mediate distinct homo-oligomerization patterns, but fibrinogen-like domains mediate ligand activity.
pubmed:affiliation
Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6142, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.