rdf-syntax-grammar
mods:
  schema location: http://www.loc.gov/mods/v3 http://www.loc.gov/standards/mods/v3/mods-3-2.xsd
  title info:
    title: Structurally specific heparan sulfate motifs dictate fibroblast growth factor signaling
    sub title: a dissertation
  name:
    name part: Luo, Yongde.
    role:
      role term: creator
  type of resource: text
  genre: abstract or summary
  origin info:
    place:
      place term: txu
    date issued: 2005
    issuance: monographic
  language:
    language term: eng
  physical description:
    form: print
    extent: xvi, 163 leaves : illustrations ; 28 cm.
  abstract: ABSTRACTS: Fibroblast growth factor (FGF) signaling is involved in development, adult homeostasis and associated diseases. Variation in size, sulfation pattern and topography of heparan sulfate (HS) oligosaccharides impacts FGF signaling by regulating the interaction of FGF with pre-formed inactive dimer of FGFRs for formation of stable active FGF-HS-FGFR signaling complex. However, whether structurally specific motifs are at play for the assembly and activation of this complex are unclear. In this report, we utilize the high-quality stable recombinant GST-FGF as a bioaffinity reagent to separate and identify oligosaccharide motifs with differential affinities for FGF and examine their ability to support FGF signaling. We isolated a rare undersulfated octasaccharide mixture (7,8-S-OctaF7) with high affinity for GST-FGF7, which forms a binary complex with FGFR2IIIb competent to subsequently bind FGF7 and activate the FGF7-linked signaling pathways with high specific activity in mouse keratinocytes expressing FGFR2IIIb, relative to the more abundant and highly sulfated octasaccharides with lower affinity. Mass spectrometric, disaccharide composition and anticoagulant activity analysis indicated that 7,8-S-OctaF7 is comprised of 7 and 8 sulfated octasaccharides exhibiting a bisulfated disaccharide containing the rare N-unsubstituted glucosamine and at least one component in which groups are distributed sufficient to support antithrombin-mediated inhibition of Factor Xa activity. However, 7,8-S-OctaF7 fails to support FGF1 signaling in both mouse fibroblasts expressing FGFR1IIIc and keratinocytes. In contrast, octasaccharides with high sulfation but lower affinity for FGF7 failing to support FGF7 signaling supports FGF1 signaling. GST-FGF1 bioaffinity fractionation revealed that FGF1 binds more oligosaccharides with high affinity than FGF7. The high affinity octasaccharides are much more heterogeneous than 7,8-S-OctaF7, and exhibit 8 or more sulfates with the most abund…
  note: by Yongde Luo.
  note: Vita.
  note: "Major Subject: Medical Sciences".
  note: "Submitted to the Graduate School of Biomedical Sciences of The Texas A&M University System Health Science Center in partial fulfillment for the requirements for the degree of Doctor of Philosophy December 2005."
  note: Approved as to style and content by: Wallace L. McKeehan, James F. Martin, Mingyao Liu, Gilbert Cote, Weimin He.
  note: Ph. D. Texas A&M University System Health Science Center 2005.
  note: Includes bibliographical references (leaves 136-162).
  subject:
    topic: Fibroblast Growth Factor 1
  subject:
    topic: Receptor, Fibroblast Growth Factor, Type 1
  subject:
    topic: Major Medical Sciences
  classification: W 4 AT4 L964s 2005
  record info:
    record content source: TMV
    record creation date: 060912
    record change date: 20191203131538.0
    record identifier: in00004502599