This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We have optimized a method that enables the characterization of structures that dictate the binding a heparan sulfate oligosaccharide to a heparin-binding protein by on-line liquid chromatography tandem mass spectrometry (LC/MS2). Heparan sulfate (HS) is a linear polysulfated polysaccharide that is localized to the cell surface and extracellular matrix. This polysaccharide plays a significant biological role by modulating the activities of a wide array of proteins including coagulation enzymes, growth factors and morphogens. Several protein binding epitopes on HS have been characterized by traditional methods such as enzymatic digestion and disaccharide analysis. Human FGF-2 (hFGF-2) is a member of the growth factor family involved in several cellular processes including proliferation, adhesion, motility and angiogenesis. FGF-2 exerts its biological function by activating signal transduction cascades after binding its receptor (FGFR) on the cell surface. The binding of FGF-2 to its receptor requires the presence of heparan sulfate (HS), a linear polysulfated polysaccharide localized to the cell surface and extracellular matrix. The presence on highly N- sulfated domains (NS domains) on this polysaccharide allows it to constitute a platform facilitating the formation of a functional FGF-FGFR complex. It is still unclear whether FGF-2 binding to these domains is dictated by the sulfate pattern or rather the sulfate density.
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