Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
The R-Spondin (RSpo) family of secreted proteins act as potent activators of the Wnt/beta-catenin signaling pathway. We have previously shown that RSpo proteins can induce proliferative effects on the gastrointestinal epithelium in mice. Here we provide a mechanism whereby RSpo1 regulates cellular responsiveness to Wnt ligands by modulating the cell-surface levels of the coreceptor LRP6. We show that RSpo1 activity critically depends on the presence of canonical Wnt ligands and LRP6. Although RSpo1 does not directly activate LRP6, it interferes with DKK1/Kremen-mediated internalization of LRP6 through an interaction with Kremen, resulting in increased LRP6 levels on the cell surface. Our results support a model in which RSpo1 relieves the inhibition DKK1 imposes on the Wnt pathway.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1965484 | PMC |
| http://dx.doi.org/10.1073/pnas.0702305104 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
LIM kinase 2 activates cardiac fibroblasts and exacerbates postinfarction left ventricular remodeling via crosstalk between the canonical and non-canonical Wnt pathways.
Pharmacol Res
October 2024
Department of Cardiology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, the Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing 210008, China; Department of Cardiology, Nanjing Drum Tower Hospital, Clinical College of Nanj
Ischemic heart failure rates rise despite decreased acute myocardial infarction (MI) mortality. Excessive myofibroblast activation post-MI leads to adverse remodeling. LIM kinases (LIMK1 and LIMK2) regulate cytoskeleton homeostasis and are pro-fibrotic markers in atrial fibrillation.
View Article and Find Full Text PDFLDL receptor-related protein 5 selectively transports unesterified polyunsaturated fatty acids to intracellular compartments.
Nat Commun
April 2024
Vascular Biology and Therapeutic Program, Yale University School of Medicine, New Haven, CT, 06520, USA.
Polyunsaturated fatty acids (PUFAs), which cannot be synthesized by animals and must be supplied from the diet, have been strongly associated with human health. However, the mechanisms for their accretion remain poorly understood. Here, we show that LDL receptor-related protein 5 (LRP5), but not its homolog LRP6, selectively transports unesterified PUFAs into a number of cell types.
View Article and Find Full Text PDFChemotherapy induces feedback up-regulation of CD44v6 in colorectal cancer initiating cells through -catenin/MDR1 signaling to sustain chemoresistance.
Front Oncol
October 2022
Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, United States.
Chemoresistance in colorectal cancer initiating cells (CICs) involves the sustained activation of multiple drug resistance (MDR) and WNT/-catenin signaling pathways, as well as of alternatively spliced-isoforms of CD44 containing variable exon-6 (CD44v6). In spite of its importance, mechanisms underlying the sustained activity of WNT/-catenin signaling have remained elusive. The presence of binding elements of the -catenin-interacting transcription factor TCF4 in the and CD44 promoters suggests that crosstalk between WNT/-catenin/TCF4-activation and the expression of the CD44v6 isoform mediated by FOLFOX, a first-line chemotherapeutic agent for colorectal cancer, could be a fundamental mechanism of FOLFOX resistance.
View Article and Find Full Text PDFExploring the mechanistic and temporal regulation of LRP6 endocytosis in canonical WNT signaling.
J Cell Sci
August 2020
Institute for Visual and Analytic Computing, Modeling and Simulation Group, Albert-Einstein-Str. 22, 18051 Rostock, Germany.
Endocytosis plays a pivotal regulatory role in canonical WNT signaling. Internalization of the low-density lipoprotein receptor-related protein 6 (LRP6) receptor complex can either promote or attenuate canonical WNT signaling, depending on the employed internalization pathway. Detailed analysis of the mechanism of LRP6 internalization and its temporal regulation is crucial for understanding the different cellular responses to WNT stimulation under varying conditions and in various cell types.
View Article and Find Full Text PDFThe tumor suppressor PTPRK promotes ZNRF3 internalization and is required for Wnt inhibition in the Spemann organizer.
Elife
January 2020
Division of Molecular Embryology, DKFZ-ZMBH Alliance, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
A hallmark of Spemann organizer function is its expression of Wnt antagonists that regulate axial embryonic patterning. Here we identify the tumor suppressor Protein tyrosine phosphatase receptor-type kappa (PTPRK), as a Wnt inhibitor in human cancer cells and in the Spemann organizer of embryos. We show that PTPRK acts via the transmembrane E3 ubiquitin ligase ZNRF3, a negative regulator of Wnt signaling promoting Wnt receptor degradation, which is also expressed in the organizer.
View Article and Find Full Text PDF