Localization of heparin-binding, neurite outgrowth and antigenic regions in midkine molecule.
Midkine is a 13kDa heparin-binding polypeptide rich in basic amino acids and cysteine and has neurite outgrowth, neuronal cell survival and other activities. We used chemically synthesized MK half molecules as well as recombinant MK deficient in N-terminal and C-terminal sequences to localize its active regions. The principal and conformation-dependent heparin-binding site was found in the C-terminal half. On the other hand, 13 amino acid residues in the C-terminal end were responsible for the MK antigenicity. The C-terminal half, but not the N-terminal half, had potent neurite outgrowth activity. However, in contrast to the whole molecule, the C-terminal half could not support the survival of embryonic brain neurons.
Muramatsu
H
H
Department of Biochemistry, Nagoya University School of Medicine, Japan.
Inui
T
T
Kimura
T
T
Sakakibara
S
S
Song
X J
XJ
Maruta
H
H
Muramatsu
T
T
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000032:analysis*; D001483:Base Sequence; D001665:Binding Sites; D001921:Brain / Q000196:embryology / Q000648:ultrastructure; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D016207:Cytokines / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D006493:Heparin / Q000378:metabolism*; D051379:Mice; D000078792:Midkine; D008969:Molecular Sequence Data; D016296:Mutagenesis; D016501:Neurites / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D000941:Antigens; D002352:Carrier Proteins; D016207:Cytokines; D000078792:Midkine; D006493:Heparin