title: Novel regulation of fibroblast growth factor 2 (FGF2)-mediated cell growth by polysialic acid.
abstract: Polysialic acid (polySia) is a unique polysaccharide that modifies neural cell adhesion molecule (NCAM) spatiotemporally. Recently, we demonstrated that polySia functions as a reservoir for several neurotrophic factors and neurotransmitters. Here, we showed the direct interaction between polySia and fibroblast growth factor-2 (FGF2) by native-PAGE, gel filtration, and surface plasmon resonance. The minimum chain length of polySia required for the interaction with FGF2 was 17. Compared with heparan sulfate, a well known glycosaminoglycan capable of forming a complex with FGF2, polySia formed a larger complex with distinct properties in facilitating oligomerization of FGF2, as well as in binding to FGF receptors. In polySia-NCAM-expressing NIH-3T3 cells, which were established by transfecting cells with either of the plasmids for the expression of the polysialyltransferases ST8SiaII/STX and ST8SiaIV/PST that can polysialylate NCAM, FGF2-stimulated cell growth, but not cell survival, was inhibited. Taken together, these results suggest that polySia-NCAM might be involved in the regulation of FGF2-FGF receptor signaling through the direct binding of FGF2 in a manner distinct from heparan sulfate.
authors.affiliation: Bioscience and Biotechnology Center and the Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Ono
authors.forename: Masaya
authors.initials: M
authors.lastname: Hane
authors.forename: Ken
authors.initials: K
authors.lastname: Kitajima
authors.forename: Chihiro
authors.initials: C
authors.lastname: Sato
mesh_terms: D000818:Animals; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D006497:Heparan Sulfate / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D041681:NIH 3T3 Cells; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D055503:Protein Multimerization / Q000502:physiology*; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism*; D012794:Sialic Acids / Q000096:biosynthesis* / Q000235:genetics; D012799:Sialyltransferases / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D016222:Fibroblast Growth Factor 2; D006497:Heparan Sulfate; D046912:Multiprotein Complexes; D019006:Neural Cell Adhesion Molecules; D017468:Receptors, Fibroblast Growth Factor; D012794:Sialic Acids; D012799:Sialyltransferases; C021319:polysialic acid; C046778:CMP-N-acetylneuraminate-poly-alpha-2,8-sialosyl sialyltransferase; C525848:ST8SiaIV protein, mouse; C515117:ST8SIA4 protein, human