Abstract
BackgroundWnt 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.ResultsHere 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.ConclusionThe 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.
Highlights
Wnt signaling is mediated through 1) the beta-catenin dependent canonical pathway and, 2) the beta-catenin independent pathways
BMC Molecular Biology 2008, 9:11 http://www.biomedcentral.com/1471-2199/9/11 ated by activation of RhoA and JNK, and the Wnt/Ca2+ pathway leads to activation of protein kinase C (PKC), calcium-calmodulin dependent kinase II (CamKII) or calcineurin (CaCN) [2,3]
To further understand the mechanism of Wnt signaling in the lung, we analyzed it in a lung carcinoma H441 cell line, which as we found in this report, has low levels of Fzd expression
Summary
Wnt signaling is mediated through 1) the beta-catenin dependent canonical pathway and, 2) the beta-catenin independent pathways. Multiple receptors, including Fzds, Lrps, Ror and Ryk, are involved in Wnt signaling. The functions of Ror in mediating the non-canonical Wnt signaling have been well established. WNT ligands are a family of secreted cysteine-rich signaling molecules that play critical roles in many cell activities, including cell fate determination, cell adhesion, cell migration and cell polarity. To activate the intracellular pathways, Wnt ligands interact with seven-span transmembrane receptor molecules known as Frizzled (Fzd), and the co-receptors from the family of low-density lipoprotein receptor-related proteins (Lrp). Wnt5a can activate or inhibit the canonical Wnt signaling depending on the availability of specific receptors [4]. Studies on the mechanism of Wnt signaling suggested that coupling of Fzd and Lrp triggers the activation of the canonical Wnt pathway [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
