Identification of novel binding sites for heparin in receptor protein-tyrosine phosphatase (RPTPσ): Implications for proteoglycan signaling
| Autor: | Ashlea A. Morgan, Nathanael J. Bangayan, Panpan Yu, Herbert M. Geller, Yasuhiro Katagiri, Radoslaw Junka |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
biology Chemistry Phosphatase Cell Biology Heparan sulfate Protein tyrosine phosphatase Immunoglobulin domain Biochemistry Cell biology 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology Proteoglycan biology.protein Chondroitin sulfate Binding site Signal transduction Molecular Biology |
| Zdroj: | Journal of Biological Chemistry. 293:11639-11647 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.ra118.003081 |
| Popis: | Receptor protein-tyrosine phosphatase RPTPσ has important functions in modulating neural development and regeneration. Compelling evidence suggests that both heparan sulfate (HS) and chondroitin sulfate (CS) glycosaminoglycans (GAGs) bind to a series of Lys residues located in the first Ig domain of RPTPσ. However, HS promotes and CS inhibits axonal growth. Mutation of these Lys residues abolished binding and signal transduction of RPTPσ to CS, whereas HS binding was reduced, and signaling persisted. This activity was mediated through novel heparin-binding sites identified in the juxtamembrane region. Although different functional outcomes of HS and CS have been previously attributed to the differential oligomeric state of RPTPσ upon GAG binding, we found that RPTPσ was clustered by both heparin and CS GAG rich in 4,6-O-disulfated disaccharide units. We propose an additional mechanism by which RPTPσ distinguishes between HS and CS through these novel binding sites. |
| Databáze: | OpenAIRE |
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