The Wnt signalling pathway is crucial in metazoans and it interacts with numerous other signalling pathways to result in the desired outcome for the cell. One of these is the receptor tyrosine kinase (RTK)–Ras–mitogen-activated protein kinase (MAPK) pathway, and this crosstalk has been extensively studied in the context of cancer. Its significance in normal development is less clear, but a recent screen by the Verheyen laboratory has shown that several of its components affect Wingless (Wg, the Drosophila Wnt homolog) in the developing larvae. In their study on page 4499, Eric Hall and Esther Verheyen now focus on the role of the kinase Downstream of Raf1 (Dsor1, a homolog of the MAPK kinase MEK proteins) in modulating Wg signalling. They demonstrate that Dsor1 promotes Wg signalling by directly interacting with Armadillo (the fly β-catenin) at the level of recruitment of the destruction complex, which prevents Arm degradation and so promotes transcription of Wg target genes. Dsor1 is activated by Ras; however, surprisingly, this does not occur through epidermal growth factor receptor (EGFR), a known activator of MAPK, but probably through insulin-like growth factor receptor. Furthermore, the authors show that this function is conserved, as mammalian MEK proteins are also able to activate Wnt signalling. Thus, in describing Dsor1/MEK as a new regulator of Wg/Wnt signalling, this work significantly enhances our understanding of signalling crosstalk during normal development and how its disruption might contribute to disease.
- © 2015. Published by The Company of Biologists Ltd