PMID- 10212223 OWN - NLM STAT- MEDLINE DCOM- 19990603 LR - 20220309 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 274 IP - 18 DP - 1999 Apr 30 TI - A receptor-like protein-tyrosine phosphatase PTPzeta/RPTPbeta binds a heparin-binding growth factor midkine. Involvement of arginine 78 of midkine in the high affinity binding to PTPzeta. PG - 12474-9 AB - Midkine is a 13-kDa heparin-binding growth factor with 45% sequence identity to pleiotrophin. Pleiotrophin has been demonstrated to bind to protein-tyrosine phosphatase zeta (PTPzeta) with high affinity. In this study, we examined the binding of midkine to PTPzeta by solid-phase binding assay. Midkine and pleiotrophin binding to PTPzeta were equally inhibited by soluble pleiotrophin and also by some specific glycosaminoglycans. For both bindings, Scatchard analysis revealed low (3.0 nM) and high (0.58 nM) affinity binding sites. These results suggested that PTPzeta is a common receptor for midkine and pleiotrophin. Midkine is structurally divided into the N- and C-terminal halves, and the latter exhibited full activity for PTPzeta binding and neuronal migration induction. The C-terminal half contains two heparin-binding sites consisting of clusters of basic amino acids, Clusters I and II. A mutation at Arg78 in Cluster I resulted in loss of the high affinity binding and reduced neuronal migration-inducing activity, while mutations at Lys83 and Lys84 in Cluster II showed almost no effect on either activity. Chondroitinase ABC-treated PTPzeta exhibited similar low affinity binding both to the native midkine and midkine mutants at Arg78. These results suggested that Arg78 in midkine plays an essential role in high affinity binding to PTPzeta by interacting with the chondroitin sulfate portion of this receptor. FAU - Maeda, N AU - Maeda N AD - Division of Molecular Neurobiology, National Institute for Basic Biology, Graduate University for Advanced Studies, Okazaki 444-8585, Japan. FAU - Ichihara-Tanaka, K AU - Ichihara-Tanaka K FAU - Kimura, T AU - Kimura T FAU - Kadomatsu, K AU - Kadomatsu K FAU - Muramatsu, T AU - Muramatsu T FAU - Noda, M AU - Noda M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Carrier Proteins) RN - 0 (Cytokines) RN - 0 (Glycosaminoglycans) RN - 0 (Nerve Tissue Proteins) RN - 0 (Receptors, Cell Surface) RN - 137497-38-2 (Midkine) RN - 9005-49-6 (Heparin) RN - 94ZLA3W45F (Arginine) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatases) RN - EC 3.1.3.48 (Ptprz1 protein, mouse) RN - EC 3.1.3.48 (Receptor-Like Protein Tyrosine Phosphatases, Class 5) SB - IM MH - Animals MH - Arginine/*metabolism MH - Carrier Proteins/chemistry/*metabolism MH - Cell Movement/drug effects MH - *Cytokines MH - Glycosaminoglycans/pharmacology MH - Heparin/*metabolism MH - Mice MH - Midkine MH - Nerve Tissue Proteins/antagonists & inhibitors/*metabolism MH - Protein Binding MH - Protein Tyrosine Phosphatases/antagonists & inhibitors/*metabolism MH - Receptor-Like Protein Tyrosine Phosphatases, Class 5 MH - Receptors, Cell Surface/*metabolism EDAT- 1999/04/23 00:00 MHDA- 1999/04/23 00:01 CRDT- 1999/04/23 00:00 PHST- 1999/04/23 00:00 [pubmed] PHST- 1999/04/23 00:01 [medline] PHST- 1999/04/23 00:00 [entrez] AID - 10.1074/jbc.274.18.12474 [doi] AID - S0021-9258(19)73378-X [pii] PST - ppublish SO - J Biol Chem. 1999 Apr 30;274(18):12474-9. doi: 10.1074/jbc.274.18.12474.