Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Query: UNIPROT:P39060 (
endostatin
)
2,284
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We have shown previously that the oligomeric
endostatin
domain of
collagen XVIII
(NC1) functioned as a motility-inducing factor regulating the extracellular matrix-dependent morphogenesis of endothelial cells. This motogenic activity gave rise to structures resembling filipodia and lamellipodia and was dependent on Rac, Cdc42, and mitogen-activated protein kinase. Here, we demonstrate that these properties of
endostatin
are primarily mediated by laminin in the basement membrane and heparan sulfates on the cell surface. The sites of interaction between laminin and oligomeric endostain include the N-terminal regions of all three laminin chains (amino acids 204-1243 of the alpha chain, 932-1161 of the beta chain, and 150-965 of the
gamma chain
). A monoclonal antibody that blocks the interactions between
endostatin
and laminin was utilized to inhibit the motogenic activity of
endostatin
. In parallel, we have engineered selective point mutations and produced recombinant forms that lack binding to heparan sulfates on the cell surface. Our data are consistent with a model of
endostatin
with two binding sites: one mainly to laminin in the basement membrane and the other to heparan sulfates on the cell surface. The two binding domains on
endostatin
appear to be separate with the possibility of some overlap between the two sites.
...
PMID:Laminin modulates morphogenic properties of the collagen XVIII endostatin domain. 1223 1
