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

Biochem Biophys Res Commun. 2000 Apr 21;270(3):936-41. doi: 10.1006/bbrc.2000.2549.

Abstract

Midkine (MK) is a heparin-binding growth factor with migration-promoting and survival-promoting activities. To identify signaling receptor(s) of MK, membrane glycoproteins with MK-binding activity were isolated from day 13 mouse embryos by lectin- and MK-affinity chromatography. SDS-PAGE followed by protein sequence analysis revealed the presence of LDL receptor-related protein (LRP) and NCAM in the fraction. The dissociation constant of binding between LRP and MK was 3.5 nM. Receptor-associated protein (RAP), which interfered with the binding, inhibited MK-dependent survival of embryonic neurons. Brushin/megalin, which is also a high molecular weight protein belonging to the LDL receptor family, bound to MK less strongly than LRP. These findings suggest that LRP is a component of the receptor complex for MK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / physiology*
  • Cytokines*
  • Embryo, Mammalian
  • Heymann Nephritis Antigenic Complex
  • Humans
  • Kinetics
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Low Density Lipoprotein Receptor-Related Protein-2
  • Membrane Glycoproteins / chemistry*
  • Membrane Glycoproteins / metabolism
  • Membrane Glycoproteins / physiology*
  • Mice
  • Midkine
  • Molecular Sequence Data
  • Nerve Growth Factors / physiology*
  • Neural Cell Adhesion Molecules / chemistry
  • Receptors, Cytokine / chemistry*
  • Receptors, Cytokine / physiology*
  • Receptors, Growth Factor / chemistry*
  • Receptors, Growth Factor / physiology*
  • Receptors, Immunologic / chemistry*
  • Recombinant Proteins / metabolism
  • Signal Transduction

Substances

  • Carrier Proteins
  • Cytokines
  • Heymann Nephritis Antigenic Complex
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Low Density Lipoprotein Receptor-Related Protein-2
  • Lrp2 protein, mouse
  • Membrane Glycoproteins
  • Nerve Growth Factors
  • Neural Cell Adhesion Molecules
  • Receptors, Cytokine
  • Receptors, Growth Factor
  • Receptors, Immunologic
  • Recombinant Proteins
  • midkine receptors
  • Midkine