ArticleThe Journal of biological chemistry2009
G Protein-coupled receptor kinases phosphorylate LRP6 in the Wnt pathway.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 67 citations in OpenAlex.
- Comparative Phosphoproteomic Profiling and Network-based Interactome Analysis of GRK5 and GRK6.Cell biochemistry and biophysics · 2026Article
- Chromosome-level genome assembly and single-cell analysis unveil molecular mechanisms of arm regeneration in the ophiuroid Ophiura sarsii vadicola.Genome biology · 2025Article
- Epigenetic regulation of individual components of combined hepatocellular-cholangiocarcinoma.PloS one · 2025Article
- A Huluwa phosphorylation switch regulates embryonic axis induction.Nature communications · 2024Article
- Promoting cardiomyocyte proliferation for myocardial regeneration in large mammals.Journal of molecular and cellular cardiology · 2024Review
- Article
- G protein-coupled receptor signaling: transducers and effectors.American journal of physiology. Cell physiology · 2022Review
- Cardiomyocyte Cell-Cycle Regulation in Neonatal Large Mammals: Single Nucleus RNA-Sequencing Data AnalysisFrontiers in bioengineering and biotechnology · 2022Article
- Non-thermal atmospheric pressure plasma activates Wnt/β-catenin signaling in dermal papilla cells.Scientific reports · 2021Article
- Regulation of the Low-Density Lipoprotein Receptor-Related Protein LRP6 and Its Association With Disease: Wnt/β-Catenin Signaling and Beyond.Frontiers in cell and developmental biology · 2021Review
- LRPs in WNT Signalling.Handbook of experimental pharmacology · 2021Review
- Mutations in GRK2 cause Jeune syndrome by impairing Hedgehog and canonical Wnt signaling.EMBO molecular medicine · 2020Article
- Arachidonic Acid Promotes Intestinal Regeneration by Activating WNT Signaling.Stem cell reports · 2020Article
- Dishevelled enables casein kinase 1-mediated phosphorylation of Frizzled 6 required for cell membrane localization.The Journal of biological chemistry · 2018Article
- G-protein-coupled receptor kinase-5 promotes glioblastoma progression by targeting the nuclear factor kappa B pathway.American journal of translational research · 2018Article
- The connections of Wnt pathway components with cell cycle and centrosome: side effects or a hidden logic?Critical reviews in biochemistry and molecular biology · 2017Review
- Dual role of GRK5 in cancer development and progression.Translational medicine @ UniSa · 2016Article
- Calcitonin Receptor-Zonula Occludens-1 Interaction Is Critical for Calcitonin-Stimulated Prostate Cancer Metastasis.PloS one · 2016Article
- The Wnt Co-Receptor Lrp5 Is Required for Cranial Neural Crest Cell Migration in Zebrafish.PloS one · 2015Article
- Updating the Wnt pathways.Bioscience reports · 2014Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Wnt ligands conduct their functions in canonical Wnt signaling by binding to two receptors, the single transmembrane low density lipoprotein receptor-related proteins 5 and 6 (LRP5/6) and seven transmembrane (7TM) Frizzled receptors. Subsequently, phosphorylation of serine/threonine residues within five repeating signature PPPSP motifs on LRP6 is responsible for LRP6 activation. GSK3beta, a cytosolic kinase for phosphorylation of a downstream effector beta-catenin, was proposed to participate in such LRP6 phosphorylation. Here, we report a new class of membrane-associated kinases for LRP6 phosphorylation. We found that G protein-coupled receptor kinases 5 and 6 (GRK5/6), traditionally known to phosphorylate and desensitize 7TM G protein-coupled receptors, directly phosphorylate the PPPSP motifs on single transmembrane LRP6 and regulate Wnt/LRP6 signaling. GRK5/6-induced LRP6 activation is inhibited by the LRP6 antagonist Dickkopf. Depletion of GRK5 markedly reduces Wnt3A-stimulated LRP6 phosphorylation in cells. In zebrafish, functional knock-down of GRK5 results in reduced Wnt signaling, analogous to LRP6 knock-down, as assessed by decreased abundance of beta-catenin and lowered expression of the Wnt target genes cdx4, vent, and axin2. Expression of GRK5 rescues the diminished beta-catenin and axin2 response caused by GRK5 depletion. Thus, our findings identify GRK5/6 as novel kinases for the single transmembrane receptor LRP6 during Wnt signaling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.