The C-type lectin domain of CD62P (P-selectin) is an integrin ligand.

CD62P (P-selectin) is confined to the inside of platelets and endothelial cells, and is translocated to the surface upon activation of platelets or endothelial cells. In current models, CD62P recognizes sialyl-Lewis X on PSGL-1 and mediates rapid rolling of leukocyte over vascular surfaces during the initial steps in inflammation. Docking simulation using integrin v{beta}3 as a target predicted that the C-type lectin domain of CD62P is a potential integrin ligand. It has not been tested if CD62P binds to integrins. Here we describe that the lectin domain of CD62P specifically bound to soluble integrins v{beta}3, IIb{beta}3, 4{beta}1 and 5{beta}1. Known inhibitors of CD62P-PSGL-1 interaction did not suppress the binding of the lectin domain to integrins. We found that the R16E/K17E mutation in the predicted integrin-binding interface of the lectin domain strongly inhibited CD62P binding to IIb{beta}3 and v{beta}3 in 1 mM Mn2+. R16E/K17E is outside of the glycan binding site. Mutating Glu-88 to Asp (the E88D mutation) in the lectin domain, which is known to strongly disrupt glycan binding, only slightly affected integrin binding, indicating that glycan binding and integrin binding sites are distinct. Also, the lectin domain of CD62P supported cell adhesion in a cation-dependent manner. CD62P-integrin interaction is potentially important since integrins are widely expressed compared to PSGL-1, which is limited to leukocytes. These findings indicate that CD62P-integrin interaction plays potentially important role in a wide variety of cell-cell interaction in addition to CD62P-glycan interaction.