Repulsive (A) versus attractive (B) outcome upon cell-contact–induced EphA/ephrin-A interactions. The studies by Wimmer-Kleikamp and coworkers, as reported in this issue of Blood, support a role for PTPases in promoting adhesion of LK63 leukemia cells to ephrin-A5 via EphA3. In a more typical (default) response such as that observed in HEK293/EphA3 cells, EphA3 activation by autophosphorylation (denoted by an asterisk) was followed by cleavage of ephrin-A5, enabling cell separation. In LK63 cells, high levels of endogenous PTPases (red circle) prevent EphA3 activation by ephrin-A5. This, together with the lack of ephrin-A5 cleavage, supports cell adhesion.