Oversulfated Chondroitin/Dermatan Sulfates Containing GlcAβ1/IdoAα1–3GalNAc(4,6-O-disulfate) Interact with L- and P-selectin and Chemokines
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We previously reported that versican, a large chondroitin/dermatan sulfate (CS/DS) proteoglycan, interacts through its CS/DS chains with adhesion molecules L- and P-selectin and CD44, as well as chemokines. Here, we have characterized these interactions further. Using a metabolic inhibitor of sulfation, sodium chlorate, we show that the interactions of the CS/DS chains of versican with L- and P-selectin and chemokines are sulfation-dependent but the interaction with CD44 is sulfation-independent. Consistently, versican's binding to L- and P-selectin and chemokines is specifically inhibited by oversulfated CS/DS chains containing GlcAbeta1-3GalNAc(4,6-O-disulfate) or IdoAalpha1-3GalNAc(4,6-O-disulfate), but its binding to CD44 is inhibited by all the CS/DS chains, including low-sulfated and unsulfated ones. Affinity and kinetic analyses using surface plasmon resonance revealed that the oversulfated CS/DS chains containing GlcAbeta1/IdoAalpha1-3GalNAc(4,6-O-disulfate) bind directly to selectins and chemokines with high affinity (K(d) 21.1 to 293 nm). In addition, a tetrasaccharide fragment of repeating GlcAbeta1-3GalNAc(4,6-O-disulfate) units directly interacts with L- and P-selectin and chemokines and oversulfated CS/DS chains containing GlcAbeta1/IdoAalpha1-3GalNAc(4,6-O-disulfate) inhibit chemokine-induced Ca(2+) mobilization. Taken together, our results show that oversulfated CS/DS chains containing GlcAbeta1/IdoAalpha1-3GalNAc(4,6-O-disulfate) are recognized by L- and P-selectin and chemokines, and imply that these chains are important in selectin- and/or chemokine-mediated cellular responses.
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- Authors
- Kawashima, H., Atarashi, K., Hirose, M., Hirose, J., Yamada, S., Sugahara, K., & Miyasaka, M.
- Affiliations
- The University of Osaka (JP)
- Kobe Pharmaceutical University (JP)
- Corresponding author
- Kawashima, Hiroto
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-04
- Volume
- 277
- Issue
- 15
- Pages
- 12921-12930
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2017704712
- Cited by
- 241
- References
- 40
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 8 · 2021: 6 · 2020: 7 · 2019: 5 · 2018: 8 · 2017: 9 · 2016: 6 · 2015: 8 · 2014: 13 · 2013: 17 · 2012: 11
- FWCI
- 6.43
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- versican, L-selectin, P-selectin, CD44, chemokine binding, calcium mobilization, cell adhesion
- MeSH terms
- Base Sequence, Chondroitin Sulfates, Dermatan Sulfate, Humans, Kinetics, Oligosaccharides, Protein Binding, DNA Primers, P-Selectin, L-Selectin
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