LDL receptor-related protein as a component of the midkine receptor

Midkine (MK) is a heparin-binding growth factor with migration-promoting an d survival-promoting activities. To identify signaling receptor(s) of MK, m embrane glycoproteins with MK-binding activity were isolated from day 13 mo use embryos by lectin- and MK-affinity chromatography, SDS-PAGE followed by protein sequence analysis revealed the presence of LDL receptor-related pr otein (LRP) and NCAM in the fraction. The dissociation constant of binding between LRP and MK was 3.5 nM. Receptor-associated protein (RAP), which int erfered with the binding, inhibited MK-dependent survival of embryonic neur ons. Brushin/megalin, which is also a high molecular weight protein belongi ng to the LDL receptor family, bound to MK less strongly than LRP. These fi ndings suggest that LRP is a component of the receptor complex for MK. (C) 2000 Academic Press.