@entity1611 ( @entity1611 ) is a strong angiogenic mitogen and plays important roles in angiogenesis under various pathophysiological conditions. The in vivo angiogenic activity of secreted @entity1611 may be regulated by extracellular inhibitors, because it is also produced in avascular tissues such as the cartilage. To seek the binding inhibitors against @entity1611 , we screened the chondrocyte cDNA library by a yeast two-hybrid system by using @entity1655 as bait and identified @entity1612 ( @entity1612 ) as a candidate. The complex formation of @entity1655 with @entity1612 was first established by immunoprecipitation from the cells overexpressing both binding partners. A competitive affinity-binding assay also demonstrated that @entity1612 binds specifically to @entity1655 with two classes of binding sites (Kd = 26 +/- 11 nM and 125 +/- 38 nM). Binding assay using deletion mutants of @entity1612 indicated that the thrombospondin type-1 repeat (TSP-1) domain of @entity1612 binds to the exon 7-coded region of @entity1655 and that the @entity1473 -terminal domain preserves the affinity to both @entity1655 and VEGF121. The interaction of @entity1655 with @entity1612 inhibited the binding of @entity1655 to the endothelial cells and the immobilized @entity11132 /IgG Fc; that is, a recombinant protein for @entity1655 receptor. By in vitro tube formation assay of endothelial cells, full-length @entity1612 and the deletion mutant possessing the TSP-1 domain inhibited @entity1655 -induced angiogenesis significantly in the complex form. This antiangiogenic activity of @entity1612 was demonstrated further by in vivo angiogenesis assay by using Matrigel injection model in @entity19 . These data demonstrate for the first time that @entity1655 binds to @entity1612 through a protein-to-protein interaction and suggest that the angiogenic activity of @entity1655 is regulated negatively by @entity1612 in the extracellular environment.

@entity1612 binds XXXX ( @entity1611 ) and inhibits @entity1611 -induced angiogenesis.

@entity11132 :: ('16542(Tax:10090)', 'Gene') :: ['KDR'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity1612 :: ('14219(Tax:10090)', 'Gene') :: ['CTGF', 'connective tissue growth factor'] @entity1655 :: ('MESH:C467484', 'Chemical') :: ['VEGF165'] @entity1611 :: ('22339(Tax:10090)', 'Gene') :: ['Vascular endothelial growth factor', 'VEGF'] @entity1473 :: ('CHEBI:46883', 'Chemical') :: ['COOH']
@entity1611 :: (22339(Tax:10090),Gene) :: ['vascular endothelial growth factor']
