Heparan Sulfate Domains Required for Fibroblast Growth Factor 1 and 2 Signaling through Fibroblast Growth Factor Receptor 1c
AuthorSchultz, Victor; Suflita, Mathew; Liu, Xinyue; Zhang, Xing; Yu, Yanlei; Li, Lingyun; Green, Dixy E.; Xu, Yongmei; Zhang, Fuming; DeAngelis, Paul L.; Liu, Jian; Linhardt, Robert J.
SubjectBiology; Chemistry and chemical biology; Chemical and biological engineering; Biomedical engineering
Full CitationHeparan Sulfate Domains Required for Fibroblast Growth Factor 1 and 2 Signaling through Fibroblast Growth Factor Receptor 1c, V. Schultz, M. Suflita, X. Liu, X. Zhang, Y. Yu, L. Li, D. E. Green, Y. Xu, F. Zhang, P. L. DeAngelis, J. Liu, R. J. Linhardt, Journal of Biological Chemistry, 292, 2495–2509, 2017.
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AbstractA 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-FGFR1c2 and FGF22-FGFR1c2 HS binding sites of the symmetric FGF2-FGFR2-HS2 signal transduction complex. The results suggest that FGF12-FGFR1c2 binding site prefers a longer NS domain at the non-reducing terminus than FGF22-FGFR1c2 In addition, FGF22-FGFR1c2 can tolerate an HS chain having an N-acetylglucosamine residue at its non-reducing end. These results clearly demonstrate the different specificity of FGF12-FGFR1c2 and FGF22-FGFR1c2 for 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.;
DescriptionHeparan Sulfate Domains Required for Fibroblast Growth Factor 1 and 2 Signaling through Fibroblast Growth Factor Receptor 1c
DepartmentThe Linhardt Research Labs.; The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS);
PublisherThe American Society for Biochemistry and Molecular Biology (ASBMB) and Elsevier
RelationshipsThe Linhardt Research Labs Online Collection; Rensselaer Polytechnic Institute, Troy, NY; Journal of Biological Chemistry; https://harc.rpi.edu/;
AccessCC BY — Creative Commons Attribution; A full text version is available in DSpace@RPI; Open Access;
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