Laminin Modulates Morphogenic Properties of the Collagen XVIII Endostatin Domain
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...
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Published in | The Journal of biological chemistry Vol. 277; no. 47; pp. 45211 - 45218 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Biochemistry and Molecular Biology
22.11.2002
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Subjects | |
Online Access | Get full text |
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Summary: | 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 204â1243 of the α chain, 932â1161 of the β chain, and 150â965 of the γ 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. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M206358200 |