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Published on: October 27, 2014
Ror2 modulates the canonical Wnt signaling in lung epithelial cells through cooperation with Fzd2
Changgong Li1, Hongyan Chen, Lingyan Hu
1Department of Pediatrics, Division of Neonatology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA. changgon@usc.edu
Background:
Wnt signaling is mediated through 1) the beta-catenin dependent canonical pathway and, 2) the beta-catenin independent pathways. Multiple receptors, including Fzds, Lrps, Ror2 and Ryk, are involved in Wnt signaling. Ror2 is a single-span transmembrane receptor-tyrosine kinase (RTK). The functions of Ror2 in mediating the non-canonical Wnt signaling have been well established. The role of Ror2 in canonical Wnt signaling is not fully understood.
Results:
Here we report that Ror2 also positively modulates Wnt3a-activated canonical signaling in a lung carcinoma, H441 cell line. This activity of Ror2 is dependent on cooperative interactions with Fzd2 but not Fzd7. In addition, Ror2-mediated enhancement of canonical signaling requires the extracellular CRD, but not the intracellular PRD domain of Ror2. We further provide evidence that the positive effect of Ror2 on canonical Wnt signaling is inhibited by Dkk1 and Krm1 suggesting that Ror2 enhances an Lrp-dependent STF response.
Conclusion:
The current study demonstrates the function of Ror2 in modulating canonical Wnt signaling. These findings support a functional scheme whereby regulation of Wnt signaling is achieved by cooperative functions of multiple mediators.
Insights
The receptor Ror2 positively influences canonical Wnt signaling in lung cancer cells, working with Fzd2. This finding clarifies Ror2
Area of Science:
- Molecular Biology
- Cell Signaling
- Cancer Research
Background:
- Wnt signaling pathways are crucial in cellular processes.
- Canonical and non-canonical Wnt pathways exist, involving various receptors.
- The precise role of Ror2 in canonical Wnt signaling remains unclear.
Purpose of the Study:
- To investigate the role of Ror2 in canonical Wnt signaling.
- To determine Ror2's interactions and domain requirements in this pathway.
Main Methods:
- Utilized H441 lung carcinoma cell line.
- Assessed Wnt3a-activated canonical signaling.
- Examined interactions with Frizzled (Fzd) receptors and domain-specific functions of Ror2.
Main Results:
- Ror2 positively modulates Wnt3a-activated canonical signaling.
- Ror2's activity depends on cooperation with Fzd2, not Fzd7.
- Extracellular CRD domain of Ror2 is essential, while the PRD domain is not.
- Dkk1 and Krm1 inhibit Ror2's positive effect, indicating an Lrp-dependent response.
Conclusions:
- Ror2 plays a role in modulating canonical Wnt signaling.
- Cooperative interactions among Wnt signaling mediators are vital for pathway regulation.
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