ArticleProceedings of the National Academy of Sciences of the United States of America2014
RSPO-LGR4 functions via IQGAP1 to potentiate Wnt signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
74 citing papers in PubMed, 111 citations in OpenAlex.
- Spatial transcriptomics reveals coordinated ventricular patterning and maturation in the developing human heart.Nature communications · 2026Article
- LGR5: from stem cell marker to therapeutic target.Trends in cancer · 2026Review
- Regulatory mechanisms of LGR4 on cancer and cancer stem cell properties.Discover oncology · 2026Review
- IQGAP3, the overlooked oncogenic twin of IQGAP1: mapping its interactome and functional roles across cellular signaling and cancer.Cell communication and signaling : CCS · 2026Review
- Investigating the relationship between osteoporosis and rheumatoid arthritis: prospective cohort study and genetic analyses.Therapeutic advances in musculoskeletal disease · 2026Article
- RSPO4 exerts tumor suppression through antagonizing canonical and non-canonical Wnt signaling.International journal of biological sciences · 2026Article
- RNF187 neddylation in pancreatic cancer activates malignancy via IQGAP1-dependent actin cytoskeleton rearrangement.Oncogene · 2026Article
- Role of Matricellular Proteins in Endothelial Cell Inflammation and Atherosclerosis.Antioxidants (Basel, Switzerland) · 2025Review
- Article
- Structural insights into Wnt/β-catenin signaling regulation by LGR4, R-spondin, and ZNRF3.Nature communications · 2025Article
- H3K4me3 regulates the transcription of RSPO3 in dermal papilla cells to influence hair follicle morphogenesis and development.Epigenetics & chromatin · 2025Article
- Distinct structural mechanisms of LGR4 modulation by Norrin and RSPOs in Wnt/β-catenin signaling.Nature communications · 2025Article
- Article
- R-spondins secreted by human pancreas-derived mesenchymal stromal cells support pancreatic organoid proliferation.Cellular and molecular life sciences : CMLS · 2025Article
- LGR4 (GPR48): The Emerging Inter-Bridge in Osteoimmunology.Biomedicines · 2025Review
- Structural insights into the LGR4-RSPO2-ZNRF3 complexes regulating WNT/β-catenin signaling.Nature communications · 2025Article
- CDC42 Regulatory Patterns Related To Inflammatory Bowel Disease and Hyperglycemia.Journal of bioinformatics and systems biology : Open access · 2025Article
- Regulation of RSPO3-LGR4 Signaling: Emerging Role in Inflammation Revealed by Network Analysis.Archives of clinical and biomedical research · 2025Article
- Expression of WNT Signaling Genes in the Dorsolateral Prefrontal Cortex in Schizophrenia.Brain sciences · 2024Article
- Targeted activation of ferroptosis in colorectal cancer via LGR4 targeting overcomes acquired drug resistance.Nature cancer · 2024Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
R-spondins (RSPOs) and their receptor leucine-rich repeat-containing G-protein coupled receptor 4 (LGR4) play pleiotropic roles in normal and cancer development as well as the survival of adult stem cells through potentiation of Wnt signaling. Current evidence indicates that RSPO-LGR4 functions to elevate levels of Wnt receptors through direct inhibition of two membrane-bound E3 ligases (RNF43 and ZNRF3), which otherwise ubiquitinate Wnt receptors for degradation. Whether RSPO-LGR4 is coupled to intracellular signaling proteins to regulate Wnt pathways remains unknown. We identified the intracellular scaffold protein IQ motif containing GTPase-activating protein 1 (IQGAP1) as an LGR4-interacting protein that mediates RSPO-LGR4's interaction with the Wnt signalosome. IQGAP1 binds to and modulates the activities of a plethora of signaling molecules, including MAP kinases, Rho GTPases, and components of the Wnt signaling pathways. Interaction of LGR4 with IQGAP1 brings RSPO-LGR4 to the Wnt signaling complex through enhanced IQGAP1-DVL interaction following RSPO stimulation. In this configuration, RSPO-LGR4-IQGAP1 potentiates β-catenin-dependent signaling by promoting MEK1/2-medidated phosphorylation of LRP5/6 as well as β-catenin-independent signaling through regulation of actin dynamics. Overall, these findings reveal that RSPO-LGR4 not only induces the clearance of RNF43/ZNRF3 to increase Wnt receptor levels but also recruits IQGAP1 into the Wnt signaling complex, leading to potent and robust potentiation of both the canonical and noncanonical pathways of Wnt signaling.
Indexed as
Identifiers
What OpenQuestion holds
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.