ROR2 Receptor Activation and Its Role in Skeletal Disorders
Author Information
Author(s): Akbarzadeh Shiva, Wheldon Lee M., Sweet Steve M. M., Talma Sonia, Mardakheh Faraz, Khosravi Heath, John K. Heath
Primary Institution: CR-UK Growth Factor Group, School of Biosciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom
Hypothesis
The study aimed to investigate the role of kinase activation in ROR2 signalling and to determine the role of the C terminal domain deleted in BDB.
Conclusion
The study found that the C-terminal domain of ROR2 is essential for its activation and that mutations in this domain lead to defective kinase activation.
Supporting Evidence
- ROR2 exhibits dimerisation-induced tyrosine kinase activity.
- Mutations in ROR2 are associated with skeletal disorders like Robinow Syndrome and Brachydactyly type B.
- Wnt5a induces phosphorylation of ROR2, confirming its role in ROR2 signalling.
- Eight sites of Src-mediated ROR2 phosphorylation were identified.
- Activation of ROR2 leads to its internalisation into Rab5 positive endosomes.
Takeaway
This study shows that a part of the ROR2 protein is needed for it to work properly, and when that part is missing, it can cause problems with bone growth.
Methodology
The study used a constitutive dimerisation approach to evaluate ROR2's kinase activity and its interaction with Src in human chondrocytes.
Digital Object Identifier (DOI)
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