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Application of a Mutant Cell Library to Determine the Structure–Function Relationship of Heparan Sulfate in Facilitating FGF2-FGFR1 Signaling

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Glycosaminoglycans

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2303))

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Abstract

Heparan sulfate (HS) is a linear polysaccharide with complex structures and modulates a wide range of biological functions. Elucidating the structure–function relationship of HS has been challenging. Recently, we generated a HS mutant mouse lung endothelial cell library by systematic deletion of HS genes expressed in the cell individually or in their combination. Here, we describe the experimental procedure using the mutant cell library to determine the structure–function relationship of HS in the regulation of FGF2-FGFR1 signaling at the levels of cell surface FGF2 binding and the downstream intracellular signaling activation. Our results demonstrated that strictly defined fine structure is required for HS to act as a co-receptor for FGF2-FGFR1 signaling.

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Acknowledgments

The research was supported by NIH R21HL131553, P41GM103390, 5R01HL093339, U01CA225784, and R56 AG062344.

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Authors and Affiliations

  1. Department of Molecular Pharmacology & Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA

    John Faulkner, Xuehong Song & Lianchun Wang

Authors
  1. John Faulkner
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  2. Xuehong Song
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  3. Lianchun Wang
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Corresponding author

Correspondence to Lianchun Wang .

Editor information

Editors and Affiliations

  1. Departments of Biology, Bioengineering, and Medicinal Chemistry, University of Utah, Salt Lake City, UT, USA

    Kuberan Balagurunathan

  2. Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN, USA

    Hiroshi Nakato

  3. Department of Medicinal Chemistry and Institute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, Richmond, VA, USA

    Umesh Desai

  4. Department of Neurobiology & Department of Nutrition & Integrative Physiology, University of Utah, Salt Lake City, UT, USA

    Yukio Saijoh

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Faulkner, J., Song, X., Wang, L. (2022). Application of a Mutant Cell Library to Determine the Structure–Function Relationship of Heparan Sulfate in Facilitating FGF2-FGFR1 Signaling. In: Balagurunathan, K., Nakato, H., Desai, U., Saijoh, Y. (eds) Glycosaminoglycans. Methods in Molecular Biology, vol 2303. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1398-6_48

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  • DOI: https://doi.org/10.1007/978-1-0716-1398-6_48

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1397-9

  • Online ISBN: 978-1-0716-1398-6

  • eBook Packages: Springer Protocols

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