LDL receptor-related protein as a component of the midkine receptor.
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.
Muramatsu
H
H
Department of Biochemistry, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
Zou
K
K
Sakaguchi
N
N
Ikematsu
S
S
Sakuma
S
S
Muramatsu
T
T
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D016207:Cytokines; D004622:Embryo, Mammalian; D026541:Heymann Nephritis Antigenic Complex; D006801:Humans; D007700:Kinetics; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D000078792:Midkine; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000502:physiology*; D019006:Neural Cell Adhesion Molecules / Q000737:chemistry; D018121:Receptors, Cytokine / Q000737:chemistry* / Q000502:physiology*; D017978:Receptors, Growth Factor / Q000737:chemistry* / Q000502:physiology*; D011971:Receptors, Immunologic / Q000737:chemistry*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction
D002352:Carrier Proteins; D016207:Cytokines; D026541:Heymann Nephritis Antigenic Complex; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D026561:Low Density Lipoprotein Receptor-Related Protein-2; C055127:Lrp2 protein, mouse; D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors; D019006:Neural Cell Adhesion Molecules; D018121:Receptors, Cytokine; D017978:Receptors, Growth Factor; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; C408049:midkine receptors; D000078792:Midkine