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Biological Description
| Specificity | ROR2 Antibody (Rabbit mAb) [A21B16] detects endogenous levels of total ROR2 protein. |
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| Background | Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a single-pass transmembrane receptor of the Ror family that carries extracellular immunoglobulin-like, cysteine-rich and Kringle domains and an intracellular tyrosine kinase domain, and it acts as a receptor or coreceptor for Wnt5a to mediate noncanonical Wnt signaling. Wnt5a binds directly to the cysteine-rich domain of ROR2, and this interaction can occur in the context of a receptor complex where ROR2 associates with Frizzled family members such as Frizzled2 or Frizzled7 via its extracellular region, forming a Wnt5a-responsive unit that regulates downstream signaling components including Dishevelled. Wnt5a stimulation induces ROR2 homodimerization and tyrosine phosphorylation in osteoblastic cells and increases phosphorylation of the scaffold protein 14‑3‑3β, demonstrating activation of a classical receptor tyrosine kinase cascade that includes direct substrate phosphorylation by ROR2 and contributes to osteoblast differentiation and bone formation. Genetic studies show that Ror2‑/‑ and Wnt5a‑/‑ mice share developmental defects including dwarfism, limb and facial abnormalities, lung and genital dysplasia and ventricular septal defects, and Wnt5a–ROR2 signaling inhibits convergent extension movements in Xenopus embryos while activating c‑Jun N‑terminal kinase, placing ROR2 in a Wnt5a‑dependent noncanonical Wnt/JNK pathway that controls morphogenetic cell movements. In hematopoietic K562 cells, Wnt5a increases ROR2 expression and induces its internalization and co-localization with Wnt5a, while ROR2 binding to Wnt5a interferes with Wnt5a association with Frizzled4 and LRP5, shifting signaling away from the β‑catenin‑dependent canonical pathway. Under these conditions, Wnt5a–ROR2 signaling regulates tyrosine phosphorylation and nuclear translocation of β‑catenin and suppresses β‑catenin/TCF-dependent transcriptional activity, with down-regulation of cyclin D1 expression, identifying a mechanism in which the Wnt5a/ROR2 noncanonical axis inhibits canonical Wnt signaling and exerts tumor-suppressive effects in leukemic models. ROR2/Fz receptor complexes also mediate Wnt5a-induced AP‑1 activation by regulating Dishevelled polymerization; ROR2 associates with Frizzled7 via its cysteine-rich domain, this complex promotes Wnt5a-triggered Dishevelled polymerization that requires both DIX and DEP domains, and polymerized Dishevelled co-localizes with Rac1 whose activity is necessary for AP‑1 promoter activation, delineating a Wnt5a–ROR2–Frizzled7–Dishevelled–Rac1–AP‑1 signaling axis. ROR2 acts as a Wnt5a-binding receptor tyrosine kinase that integrates extracellular Wnt5a gradients into noncanonical signaling outputs involving JNK, Rac1 and AP‑1, while modulating β‑catenin activity and cyclin D1 expression, and its roles in skeletal morphogenesis, osteoblast differentiation and regulation of canonical Wnt signaling underpin its relevance as a target in developmental biology and in tumor contexts where Wnt5a/ROR2 signaling contributes to migration, invasion or suppression of β‑catenin-driven transcription. |
Usage Information
| Application | IHC | Dilution |
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| Reactivity | Human | ||||
| Source | Rabbit Monoclonal Antibody | MW | 105 kDa | ||
| Storage Buffer | PBS, pH 7.2+50% Glycerol+0.05% BSA+0.01% NaN3 | Storage (from the date of receipt) |
-20°C (avoid freeze-thaw cycles), 2 years | ||
References
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