@entity9615 mediates diverse responses in vascular cells, ranging from cell adhesion, migration, and proliferation to uptake of adenoviruses. However, the extent to which alpha(V)beta(3) is regulated by changes in receptor conformation (affinity), receptor diffusion/clustering (avidity), or post-receptor events is unknown. Affinity regulation of the related integrin, alpha(IIb)beta(3), has been established using a monovalent ligand-mimetic antibody, @entity26279 @entity1334 . To determine the role of affinity modulation of alpha(V)beta(3), a novel monovalent ligand-mimetic antibody (WOW-1) was created by replacing the heavy chain hypervariable region 3 of @entity26279 @entity1334 with a single alpha(V) integrin-binding domain from multivalent adenovirus penton base. Both WOW-1 @entity1334 and penton base bound selectively to activated alpha(V)beta(3), but not to alpha(IIb)beta(3), in receptor and cell binding assays. alpha(V)beta(3) affinity varied with the cell type. Unstimulated B-lymphoblastoid cells bound WOW-1 @entity1334 poorly (apparent K(d) = 2.4 microM), but acute stimulation with @entity1359 increased receptor affinity >30-fold (K(d) = 80 nM), with no change in receptor number. In contrast, alpha(V)beta(3) in @entity320 cells was constitutively active, but ligand binding could be suppressed by overexpression of beta(3) cytoplasmic tails. Up-regulation of alpha(V)beta(3) affinity had functional consequences in that it increased cell adhesion and spreading and promoted adenovirus-mediated gene transfer. These studies establish that alpha(V)beta(3) is subject to rapid regulated changes in affinity that influence the biological functions of this integrin.

Mechanisms and consequences of affinity modulation of XXXX detected with a novel patch-engineered monovalent ligand.

@entity26279 :: ('117', 'Gene') :: ['PAC1'] @entity1359 :: ('CHEBI:37537', 'Chemical') :: ['phorbol 12-myristate 13-acetate'] @entity1334 :: ('2187', 'Gene') :: ['Fab'] @entity320 :: ('MESH:D008545', 'Disease') :: ['melanoma'] @entity9615 :: ('3685', 'Gene') :: ['Integrin alpha(V)beta(3)']
@entity9615 :: (3685,Gene) :: ['integrin alpha(V)beta(3)']
