title: Specific molecular interactions of oversulfated chondroitin sulfate E with various heparin-binding growth factors. Implications as a physiological binding partner in the brain and other tissues.
abstract: We previously observed that the cortical neuronal cell adhesion mediated by midkine (MK), a heparin (Hep)-binding growth factor, is specifically inhibited by oversulfated chondroitin sulfate-E (CS-E) (Ueoka, C., Kaneda, N., Okazaki, I., Nadanaka, S., Muramatsu, T., and Sugahara, K. (2000) J. Biol. Chem. 275, 37407-37413) and that CS-E exhibits neurite outgrowth promoting activities toward embryonic rat hippocampal neurons. We have also shown oversulfated CS chains in embryonic chick and rat brains and demonstrated that the CS disaccharide composition changes during brain development. In view of these findings, here we tested the possibility of CS-E interacting with Hep-binding growth factors during development, using squid cartilage CS-E. The binding ability of Hep-binding growth factors (MK, pleiotrophin (PTN), fibroblast growth factor-1 (FGF-1), FGF-2, Hep-binding epidermal growth factor-like growth factor (HB-EGF), FGF-10, FGF-16, and FGF-18) toward [(3)H]CS-E was first tested by a filter binding assay, which demonstrated direct binding of all growth factors, except FGF-1, to CS-E. The bindings were characterized further in an Interaction Analysis system, where all of the growth factors, except FGF-1, gave concentration-dependent and specific bindings. The kinetic constants k(a), k(d), and K(d) suggested that MK, PTN, FGF-16, FGF-18, and HB-EGF bound strongly to CS-E, in comparable degrees to the binding to Hep, whereas the intensity of binding of FGF-2 and FGF-10 toward CS-E was lower than that for Hep. These findings suggest the possibility of CS-E being a binding partner, a coreceptor, or a genuine receptor for various Hep-binding growth factors in the brain and possibly also in other tissues.
authors.affiliation: Department of Biochemistry, Kobe Pharmaceutical University, Higashinada-ku, Japan.
authors.forename: Sarama Sathyaseelan
authors.initials: SS
authors.lastname: Deepa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Umehara
authors.forename: Shigeki
authors.initials: S
authors.lastname: Higashiyama
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Itoh
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Sugahara
mesh_terms: D000818:Animals; D019921:Biotinylation; D001921:Brain / Q000378:metabolism*; D002356:Cartilage / Q000378:metabolism; D002809:Chondroitin Sulfates / Q000235:genetics* / Q000378:metabolism*; D049832:Decapodiformes; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000378:metabolism; D051526:Fibroblast Growth Factor 10; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D051379:Mice; D011485:Protein Binding; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors
chemical_list: C496463:FGF10 protein, human; C496464:Fgf10 protein, mouse; C496465:Fgf10 protein, rat; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D011994:Recombinant Proteins; C038142:chondroitin sulfate glycosaminoglycan; C113569:fibroblast growth factor 18; D016222:Fibroblast Growth Factor 2; D005346:Fibroblast Growth Factors; D006493:Heparin; D002809:Chondroitin Sulfates