LOCALIZATION OF HEPARIN-BINDING, NEURITE OUTGROWTH AND ANTIGENIC REGIONS IN MIDKINE MOLECULE

Midkine is a 13kDa heparin-binding polypeptide rich in basic amino aci ds 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 sequence s to localize its active regions. The principal and conformation-depen dent heparin-binding site was found in the C-terminal half. On the oth er 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 t he whole molecule, the C-terminal half could not support the survival of embryonic brain neurons. (C) 1994 Academic Press, Inc.