Abstract
The Ryk receptor belongs to the atypical receptor tyrosine kinase family. It is a new member of the family of Wnt receptor proteins. However, the molecular mechanisms by which the Ryk receptor functions remain unknown. Here, we report that mammalian Ryk, unlike the Drosophila Ryk homolog Derailed, functions as a coreceptor along with Frizzled for Wnt ligands. Ryk also binds to Dishevelled, through which it activates the canonical Wnt pathway, providing a link between Wnt and Dishevelled. Transgenic mice expressing Ryk siRNA exhibit defects in axon guidance, and Ryk is required for neurite outgrowth induced by Wnt-3a and in the activation of T cell factor (TCF) induced by Wnt-1. Thus, Ryk appears to play a crucial role in Wnt-mediated signaling.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing
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Animals
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Cell Differentiation / genetics*
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Cell Line
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Central Nervous System / cytology
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Central Nervous System / embryology*
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Central Nervous System / metabolism
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Dishevelled Proteins
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Drosophila Proteins
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Embryo, Mammalian / cytology
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Embryo, Mammalian / embryology*
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Embryo, Mammalian / metabolism
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Frizzled Receptors
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Genes, Regulator / genetics
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Growth Cones / metabolism*
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Growth Cones / ultrastructure
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Humans
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Lymphoid Enhancer-Binding Factor 1
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Macromolecular Substances
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Mice
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Mice, Transgenic
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Phosphoproteins
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Protein Binding / genetics
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Protein Structure, Tertiary / genetics
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Proteins / genetics
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Proteins / metabolism
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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RNA, Small Interfering
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Receptor Protein-Tyrosine Kinases / genetics
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Receptor Protein-Tyrosine Kinases / metabolism*
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Receptors, G-Protein-Coupled
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Receptors, Neurotransmitter / genetics
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Receptors, Neurotransmitter / metabolism
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Wnt Proteins
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Wnt1 Protein
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Wnt3 Protein
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Wnt3A Protein
Substances
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Adaptor Proteins, Signal Transducing
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DNA-Binding Proteins
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Dishevelled Proteins
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Drosophila Proteins
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Frizzled Receptors
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Fzd1 protein, mouse
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Lymphoid Enhancer-Binding Factor 1
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Macromolecular Substances
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Phosphoproteins
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Proteins
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Proto-Oncogene Proteins
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RNA, Small Interfering
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Receptors, G-Protein-Coupled
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Receptors, Neurotransmitter
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Transcription Factors
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WNT1 protein, human
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WNT3A protein, human
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Wnt Proteins
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Wnt1 Protein
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Wnt1 protein, mouse
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Wnt3 Protein
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Wnt3A Protein
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Wnt3a protein, mouse
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dsh protein, Drosophila
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Receptor Protein-Tyrosine Kinases
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Ryk protein, mouse