Synergistic Binding of XXXX and its Receptors to Heparin Selectively Modulates Complex Affinity.

@entity12867 @entity7 @entity319 @entity1655 @entity6758 @entity1366 @entity597
UNASSIGNED: Angiogenesis is a highly regulated process orchestrated by the @entity7 system. Heparin/heparan @entity597 (HS) proteoglycans and @entity12867 ( @entity12867 ) have been identified as co-receptors, yet the mechanisms of action have not been fully defined. In the present study we characterized molecular interactions between receptors and co-receptors, using surface plasmon resonance (SPR) and in vitro binding assays. Additionally, we demonstrate these binding events are relevant to @entity7 activity witihin endothelial cells. We defined interactions and structural requirements for heparin/HS interactions with @entity6758 ( @entity6758 ), @entity12867 , and @entity1655 in complex with @entity319 and @entity12867 . We demonstrate that these structural requirements are distinct for each interaction. We further show that @entity1655 , @entity319 and monomeric @entity12867 bind weakly to heparin alone, yet show synergistic binding to heparin when presented together in various combinations. This synergistic binding appears to translate to alterations in @entity7 signaling in endothelial cells. We found that soluble @entity12867 increases @entity7 binding and activation of @entity319 and @entity1366 in endothelial cells, and that these effects require sulfated HS. These data suggest that the presence of HS/heparin and @entity12867 may dictate the specific receptor type activated by @entity7 and ultimately determine the biological output of the system. The ability of co-receptors to fine-tune @entity7 responsiveness suggests the possibility that @entity7 -mediated angiogenesis can be selectively stimulated or inhibited by targeting HS/heparin and @entity12867 .
