(A) At cell-cell boundaries, ephrin receptor/ephrin ligand complexes regulate cellular adhesion and signaling, including ligand-induced outside-in signaling of αIIbβ3. (B) Compared with wild-type, a newly identified Arg745Cys (R745C) mutation in the tyrosine kinase domain of EPHB2 is associated with impaired platelet activation in response to agonists acting at G protein-coupled receptors (GPCRs) or glycoprotein VI (GPVI) and attenuated phosphorylation of Lyn, Syk, and FcRγ and inside-out activation of αIIbβ3. See the text for details and references.