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The kinase-null EphB6 receptor undergoes transphosphorylation in a complex with EphB1
Andrew Freywald1, Nigel Sharfe, Chaim M Roifman
1Immunology and Allergy, Department of Paediatrics, Infection, Immunity, Injury and Repair Program, Research Institute, The Hospital for Sick Children and the University of Toronto, Toronto M5G 1X8, Canada.
The Journal of Biological Chemistry
|November 20, 2001
Summary
Despite lacking kinase activity, EphB6 receptors undergo inducible tyrosine phosphorylation and form signaling complexes. This study reveals EphB6
Area of Science:
- Cellular signaling
- Receptor tyrosine kinases
- Molecular biology
Background:
- EphB6 receptor tyrosine kinase is catalytically inactive.
- Its role in cytoplasmic signaling has been uncertain.
- Eph receptors mediate cell-cell interactions.
Purpose of the Study:
- To investigate EphB6 signaling despite its inactive kinase domain.
- To explore cross-talk between Eph receptors.
- To identify EphB6-interacting proteins.
Main Methods:
- Stimulation of EphB6 with ephrin-B1.
- Overexpression of catalytically active EphB1.
- Co-immunoprecipitation assays to detect protein complexes.
- Analysis of EphB6 and c-Cbl association.
Main Results:
- EphB6 undergoes inducible tyrosine phosphorylation upon ephrin-B1 stimulation.
- EphB1 overexpression leads to ligand-dependent EphB6 transphosphorylation.
- EphB1 and EphB6 form a stable hetero-complex.
- Proto-oncogene c-Cbl constitutively binds EphB6 via its phosphotyrosine binding domain.
Conclusions:
- EphB6 is an actively signaling receptor capable of transphosphorylation.
- EphB6 initiates specific cytoplasmic signaling events.
- Cross-talk between Eph receptors contributes to signaling pathways.