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Mindbomb 1, an E3 ubiquitin ligase, forms a complex with RYK to activate Wnt/β-catenin signaling
- Source :
- The Journal of Cell Biology
- Publication Year :
- 2011
- Publisher :
- Rockefeller University Press, 2011.
-
Abstract
- MIB1 ubiquitin ligase–mediated regulation of internalization of the Wnt receptor RYK is necessary for response to Wnt3a ligand in cell culture and C. elegans.<br />Receptor-like tyrosine kinase (RYK) functions as a transmembrane receptor for the Wnt family of secreted protein ligands. Although RYK undergoes endocytosis in response to Wnt, the mechanisms that regulate its internalization and concomitant activation of Wnt signaling are unknown. We discovered that RYK both physically and functionally interacts with the E3 ubiquitin ligase Mindbomb 1 (MIB1). Overexpression of MIB1 promotes the ubiquitination of RYK and reduces its steady-state levels at the plasma membrane. Moreover, we show that MIB1 is sufficient to activate Wnt/β-catenin (CTNNB1) signaling and that this activity depends on endogenous RYK. Conversely, in loss-of-function studies, both RYK and MIB1 are required for Wnt-3A–mediated activation of CTNNB1. Finally, we identify the Caenorhabditis elegans orthologue of MIB1 and demonstrate a genetic interaction between ceMIB and lin-18/RYK in vulva development. These findings provide insights into the mechanisms of Wnt/RYK signaling and point to novel targets for the modulation of Wnt signaling.
- Subjects :
- Leupeptins
Gene Expression
Mice
0302 clinical medicine
Ubiquitin
Protein Interaction Mapping
Phosphorylation
RNA, Small Interfering
Wnt Signaling Pathway
Research Articles
beta Catenin
0303 health sciences
biology
Wnt signaling pathway
Chloroquine
3. Good health
Cell biology
Ubiquitin ligase
DNA-Binding Proteins
Protein Transport
Low Density Lipoprotein Receptor-Related Protein-6
030220 oncology & carcinogenesis
embryonic structures
Female
Signal transduction
Proteasome Inhibitors
Tyrosine kinase
Protein Binding
Signal Transduction
Proteasome Endopeptidase Complex
animal structures
Beta-catenin
Ubiquitin-Protein Ligases
education
Transfection
Article
03 medical and health sciences
Cell Line, Tumor
Wnt3A Protein
Animals
Humans
Protein Interaction Domains and Motifs
Caenorhabditis elegans
Caenorhabditis elegans Proteins
rab5 GTP-Binding Proteins
030304 developmental biology
Endosomal Sorting Complexes Required for Transport
Cell Membrane
Ubiquitination
Animal Structures
Receptor Protein-Tyrosine Kinases
Intracellular Membranes
Cell Biology
Wnt Proteins
HEK293 Cells
Mutation
biology.protein
Amyloid Precursor Protein Secretases
Lysosomes
HeLa Cells
Transcription Factors
Subjects
Details
- ISSN :
- 15408140 and 00219525
- Volume :
- 194
- Database :
- OpenAIRE
- Journal :
- Journal of Cell Biology
- Accession number :
- edsair.doi.dedup.....6133600153bb3a7bbc0b733f968eed0c