Tyrosine Phosphorylation of LRP6 and its role in regulation Wnt signaling

• Antragsteller: Dr. Gary Davidson
• Fachliche Zuordnung: Entwicklungsbiologie
• Förderung: Förderung von 2012 bis 2016
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 58160712

Metazoans use Wnt/β-catenin signaling to control critical aspects of cell behavior and deregulated Wnt signaling is strongly implicated in human disease. We perform cell culturebased expression screening to identify new modifiers that effect specific Wnt pathway components. A key focus of our work is to understand how cells control reception of Wnt signaling via low-density lipoprotein receptor-related-protein 6 (LRP6). Although serine and threonine phosphorylation has been well studied, the potential role of tyrosine phosphorylation of LRP6 has not been investigated. Using pan phospho-specific antibodies we screened a kinase cDNA library by SDS-PAGE / Immunoblot analysis and identified a novel LRP6 tyrosine kinase. Preliminary work demonstrates that it specifically interacts with LRP6, inhibits LRP6/Wnt signaling and is itself regulated by Wnt signaling. These finding indicate that tyrosine phosphorylation of LRP6 plays an important role in regulating Wnt signaling. Here we propose to analyze in detail how this kinase functions to regulate LRP6, using molecular biology, cell biology as well as in-vivo experiments. Biochemical experiments will be performed using cell culture and physiological relevance will be addressed using both zebrafish and Xenopus.

• DFG-Verfahren: Forschungsgruppen
• Teilprojekt zu: FOR 1036: Mechanisms, functions and evolution of Wnt-signaling pathways