Midkine binds to 37-kDa laminin binding protein precursor, leading to nuclear transport of the complex.
Midkine (MK) is a heparin binding multifunctional protein that promotes cell survival and cell migration. MK was found to bind to 37-kDa laminin binding protein precursor (LBP), a precursor of 67-kDa laminin receptor, with K(d) of 1.1 nM between MK and LBP-glutathione-S-transferase fusion protein. The binding was inhibited by laminin, anti-LBP, amyloid beta-peptide, and heparin; the latter two are known to bind to MK. In CMT-93 mouse rectal carcinoma cells, LBP was mostly located in the cytoplasm as revealed by immunostaining with anti-LBP antibody. That a portion of LBP or 67-kDa laminin receptor was located at the surface of these cells was verified by inhibition of cell attachment to laminin-coated dishes by anti-LBP antibody. When MK was added to culture medium of these cells, a part of LBP migrated to the nucleus. The movement occurred concomitantly with nuclear transport of biotin-labeled MK. These findings suggested that the binding of MK to LBP caused nuclear translocation of the molecular complex.
Salama
R H
RH
Department of Biochemistry, Nagoya University School of Medicine, 65 Tsurumai-cho, Nagoya, Showa-ku, 466-8550, Japan.
Muramatsu
H
H
Zou
K
K
Inui
T
T
Kimura
T
T
Muramatsu
T
T
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D002522:Chlorocebus aethiops; D016207:Cytokines; D006801:Humans; D051379:Mice; D000078792:Midkine; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000378:metabolism*; D017474:Receptors, Laminin / Q000378:metabolism*; D013347:Subcellular Fractions; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D016207:Cytokines; D011498:Protein Precursors; D017474:Receptors, Laminin; D000078792:Midkine