Surface densities of ephrin-B1 determine EphB1-coupled activation of cell attachment through alpha(v)beta(3) and alpha(5)beta(1) integrins

Receptors of the Eph family and their ligands (ephrins) mediate development al vascular assembly and direct axonal guidance. Migrating cell processes i dentify appropriate targets within migratory fields based on topographicall y displayed ephrin gradients. Here, EphB1 regulated cell attachment by disc riminating the density at which ephrin-B1 was displayed on a reconstituted surface. EphB1-ephrin-B1 engagement did not promote cell attachment through mechanical tethering, but did activate integrin-mediated attachment, In en dothelial cells, attachment to RGD peptides or fibrinogen was mediated thro ugh alpha(v)beta(3) integrin. EphB1 transfection conferred ephrin-B1-respon sive activation of alpha(5)beta(1) integrin-mediated cell attachment in hum an embryonic kidney cells. Activation-competent but signaling-defective Eph B1 point mutants failed to stimulate ephrin-B1 dependent attachment. These findings lead us to propose that EphB1. functions as a 'ligand density sens or' to signal integrin-mediated cell-matrix attachment.