Biochemical and functional characterization of the Ror2/BRIb receptor complex.
Ror2 belongs to the Ror family of receptor tyrosine kinases. Two distinct human disorders result from mutations in Ror2 suggesting a role in cartilage formation, chondrocyte differentiation, and joint formation. We have previously demonstrated functional and physical association of Ror2 with the BMP receptor type Ib (BRIb). The interaction site was mapped to the extracellular CRD domain of Ror2. Here we show specific association with and transphosphorylation by BRIb, but not BMP receptors Ia or II. This association is independent of N-glycosylation, excluding the possibility that the interaction is mediated by carbohydrate moieties present in the CRD region of Ror2. The Ror2/BRIb complex proved very stable under high ionic and reducing conditions, yet it appeared sensitive to SDS-treatment. Besides we provide evidence that the Ror2/BRIb complex forms in distinct microdomains at the plasma membrane (DRMs), indicating that Ror2 may interfere with BMP signaling complexes within these membrane domains.
Sammar
Marei
M
Ort Braude College, Karmiel, Israel.
Sieber
Christina
C
Knaus
Petra
P
D000818:Animals; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000378:metabolism*; D019556:COS Cells; D002241:Carbohydrates / Q000737:chemistry; D002522:Chlorocebus aethiops; D004220:Disulfides / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D047468:Immunoprecipitation; D021962:Membrane Microdomains / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*
D002241:Carbohydrates; D004220:Disulfides; D011956:Receptors, Cell Surface; C078717:ROR2 protein, human; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D052005:Bone Morphogenetic Protein Receptors, Type I