Characterization of wise protein and its molecular mechanism to interact with both Wnt and BMP signals
| Autor: | José W. Saldanha, Katherine B. Lintern, Alison Rowe, Sonia Guidato, Nobue Itasaki |
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| Rok vydání: | 2009 |
| Předmět: |
Models
Molecular animal structures Glycosylation Immunoprecipitation Blotting Western Plasma protein binding Bone Morphogenetic Protein 4 Biology Bone morphogenetic protein Biochemistry Cell Line Mice Animals Humans Molecular Biology LDL-Receptor Related Proteins Cystine knot Mechanisms of Signal Transduction Wnt signaling pathway LRP6 Cell Biology Cell biology Protein Structure Tertiary Wnt Proteins Bone morphogenetic protein 4 embryonic structures Bone Morphogenetic Proteins Mutation Proteoglycans Signal transduction Chickens Protein Binding Signal Transduction |
| Zdroj: | The Journal of biological chemistry. 284(34) |
| ISSN: | 1083-351X |
| Popis: | Cross-talk of BMP and Wnt signaling pathways has been implicated in many aspects of biological events during embryogenesis and in adulthood. A secreted protein Wise and its orthologs (Sostdc1, USAG-1, and Ectodin) have been shown to modulate Wnt signaling and also inhibit BMP signals. Modulation of Wnt signaling activity by Wise is brought about by an interaction with the Wnt co-receptor LRP6, whereas BMP inhibition is by binding to BMP ligands. Here we have investigated the mode of action of Wise on Wnt and BMP signals. It was found that Wise binds LRP6 through one of three loops formed by the cystine knot. The Wise deletion construct lacking the LRP6-interacting loop domain nevertheless binds BMP4 and inhibits BMP signals. Moreover, BMP4 does not interfere with Wise-LRP6 binding, suggesting separate domains for the physical interaction. Functional assays also show that the ability of Wise to block Wnt1 activity through LRP6 is not impeded by BMP4. In contrast, the ability of Wise to inhibit BMP4 is prevented by additional LRP6, implying a preference of Wise in binding LRP6 over BMP4. In addition to the interaction of Wise with BMP4 and LRP6, the molecular characteristics of Wise, such as glycosylation and association with heparan sulfate proteoglycans on the cell surface, are suggested. This study helps to understand the multiple functions of Wise at the molecular level and suggests a possible role for Wise in balancing Wnt and BMP signals. |
| Databáze: | OpenAIRE |
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