title: Heparan Sulfate Domains Required for Fibroblast Growth Factor 1 and 2 Signaling through Fibroblast Growth Factor Receptor 1c.
abstract: A small library of well defined heparan sulfate (HS) polysaccharides was chemoenzymatically synthesized and used for a detailed structure-activity study of fibroblast growth factor (FGF) 1 and FGF2 signaling through FGF receptor (FGFR) 1c. The HS polysaccharide tested contained both undersulfated (NA) domains and highly sulfated (NS) domains as well as very well defined non-reducing termini. This study examines differences in the HS selectivity of the positive canyons of the FGF12-FGFR1c2and FGF22-FGFR1c2HS binding sites of the symmetric FGF2-FGFR2-HS2signal transduction complex. The results suggest that FGF12-FGFR1c2binding site prefers a longer NS domain at the non-reducing terminus than FGF22-FGFR1c2In addition, FGF22-FGFR1c2can tolerate an HS chain having anN-acetylglucosamine residue at its non-reducing end. These results clearly demonstrate the different specificity of FGF12-FGFR1c2and FGF22-FGFR1c2for well defined HS structures and suggest that it is now possible to chemoenzymatically synthesize precise HS polysaccharides that can selectively mediate growth factor signaling. These HS polysaccharides might be useful in both understanding and controlling the growth, proliferation, and differentiation of cells in stem cell therapies, wound healing, and the treatment of cancer.
authors.affiliation: From the Departments of Chemistry and Chemical Biology.
authors.forename: Victor
authors.initials: V
authors.lastname: Schultz
authors.affiliation: Biology.
authors.forename: Mathew
authors.initials: M
authors.lastname: Suflita
authors.affiliation: From the Departments of Chemistry and Chemical Biology.
authors.forename: Xinyue
authors.initials: X
authors.lastname: Liu
authors.affiliation: From the Departments of Chemistry and Chemical Biology.
authors.forename: Xing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: From the Departments of Chemistry and Chemical Biology.
authors.forename: Yanlei
authors.initials: Y
authors.lastname: Yu
authors.affiliation: the Wadsworth Center, New York State Department of Health, Albany, New York 12201.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Li
authors.affiliation: the Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73126, and.
authors.forename: Dixy E
authors.initials: DE
authors.lastname: Green
authors.affiliation: the Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Xu
authors.affiliation: From the Departments of Chemistry and Chemical Biology.
authors.forename: Fuming
authors.initials: F
authors.lastname: Zhang
authors.affiliation: the Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73126, and.
authors.forename: Paul L
authors.initials: PL
authors.lastname: DeAngelis
authors.affiliation: the Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: From the Departments of Chemistry and Chemical Biology, linhar@rpi.edu.|Biology.|Biomedical Engineering, and.|Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York 12180.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Linhardt
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism*; D013058:Mass Spectrometry; D051379:Mice; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D016220:Fibroblast Growth Factor 1; D016222:Fibroblast Growth Factor 2; D006497:Heparan Sulfate; D051496:Receptor, Fibroblast Growth Factor, Type 1; C496349:Fgfr1 protein, mouse
keywords: block copolymers; domain structures; fibroblast growth factor (FGF); fibroblast growth factor receptor (FGFR); heparan sulfate; signaling; structure-function