ArticleMolecular endocrinology (Baltimore, Md.)2009
Inhibition of WNT signaling by G protein-coupled receptor (GPCR) kinase 2 (GRK2).
Article in Molecular endocrinology (Baltimore, Md.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Recent advances in the development of GRK2 inhibitors: blocking the interaction of GRK2 with its partners.Acta pharmacologica Sinica · 2026Review
- Regulation of G protein-coupled receptor kinase 2 and its role in tumors.Journal of translational medicine · 2026Review
- The function of GPCRs in different bone cells.International journal of biological sciences · 2025Review
- Reanalysis of Whole-Exome Sequencing Data of an Infant with Suspected Diagnosis of Jeune Syndrome Revealed a Likely Pathogenic Variant inMolecular syndromology · 2024Article
- Protein proximity networks and functional evaluation of the casein kinase 1 gamma family reveal unique roles for CK1γ3 in WNT signaling.The Journal of biological chemistry · 2022Article
- Mutations in GRK2 cause Jeune syndrome by impairing Hedgehog and canonical Wnt signaling.EMBO molecular medicine · 2020Article
- G protein-coupled receptor kinase 2 (GRK2) as a multifunctional signaling hub.Cellular and molecular life sciences : CMLS · 2019Review
- The role of G protein-coupled receptor kinases in the pathology of malignant tumors.Acta pharmacologica Sinica · 2018Review
- GRK5 - A Functional Bridge Between Cardiovascular and Neurodegenerative Disorders.Frontiers in pharmacology · 2018Review
- Downregulation of RIKP by miR-200a promotes the invasive ability of esophageal cancer cells by upregulating the expression of LIN28 and MMP-14.International journal of clinical and experimental pathology · 2017Article
- Multiple functions of G protein-coupled receptor kinases.Journal of molecular signaling · 2014Article
- Role of regulator of G protein signaling proteins in bone.Frontiers in bioscience (Landmark edition) · 2014Review
- Mechanisms of the proteinuria induced by Rho GTPases.Kidney international · 2012Article
- Technical phosphoproteomic and bioinformatic tools useful in cancer research.Journal of clinical bioinformatics · 2011Article
- Calcineurin (CN) activation promotes apoptosis of glomerular podocytes both in vitro and in vivo.Molecular endocrinology (Baltimore, Md.) · 2011Article
- Wnt11 promotes cardiomyocyte development by caspase-mediated suppression of canonical Wnt signals.Molecular and cellular biology · 2011Article
- Regulation of Lrp6 phosphorylation.Cellular and molecular life sciences : CMLS · 2010Review
- Development of small molecules targeting the Wnt pathway for the treatment of colon cancer: a high-throughput screening approach.American journal of physiology. Gastrointestinal and liver physiology · 2010Review
- The complex G protein-coupled receptor kinase 2 (GRK2) interactome unveils new physiopathological targets.British journal of pharmacology · 2010Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Activation of Wnt signaling pathways causes release and stabilization of the transcription regulator beta-catenin from a destruction complex composed of axin and the adenomatous polyposis coli (APC) protein (canonical signaling pathway). Assembly of this complex is facilitated by a protein-protein interaction between APC and a regulator of G protein signaling (RGS) domain in axin. Because G protein-coupled receptor kinase 2 (GRK2) has a RGS domain that is closely related to the RGS domain in axin, we determined whether GRK2 regulated canonical signaling. We found that GRK2 inhibited Wnt1-induced activation of a reporter construct as well as reduced Wnt3a-dependent stabilization and nuclear translocation of beta-catenin. GRK2 enzymatic activity was required for this negative regulatory effect, and depletion of endogenous GRK2 using small interfering RNA enhanced canonical signaling. GRK2-dependent inhibition of canonical signaling is relevant to osteoblast (OB) biology because overexpression of GRK2 attenuated Wnt/beta-catenin signaling in calvarial OBs. Coimmunoprecipitation studies found that: 1) GRK2 bound APC; 2) The GRK2-APC interaction was promoted by GRK2 enzymatic activity; and 3) Deletion of the RGS domain in GRK2 prevented both the GRK2-APC interaction and GRK2-dependent inhibition of canonical signaling. These data suggest that: 1) GRK2 negatively regulates Wnt signaling; 2) GRK2-dependent inhibition of canonical signaling requires a protein-protein interaction between the RGS domain in GRK2 and APC; and 3) Enzymatic activity promotes the GRK2-APC interaction and is required for the negative regulatory effect on canonical signaling. We speculate that inhibiting GRK2 activity in bone-forming OBs might be a useful therapeutic strategy for increasing bone mass.
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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.