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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Bang, Anne G. Schultz, Peter G. Chanda, Sumit K. Ding, Sheng Kintner, Chris Liu, Jun Orth, Anthony P. |
| Description | Author Affiliation: Liu J ( Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.); |
| Abstract | The Wnt signaling pathway acts ubiquitously in metazoans to control various aspects of embryonic development. Wnt ligands bind their receptors Frizzled and low-density lipoprotein receptor-related protein 5/6 and function through Disheveled (Dvl), Axin, adenomatous polyposis coli, glycogen synthase kinase 3beta, and casein kinase (CK) 1 to stabilize beta-catenin and induce lymphocyte enhancer-binding factor (LEF)/T cell factor (TCF)-dependent transcriptional activities. To identify previously unrecognized Wnt signaling modulators, a genome-wide functional screen was performed using large-scale arrayed cDNA collections. From this screen, both known components and previously uncharacterized regulators of this pathway were identified, including beta-catenin, Dvl1, Dvl3, Fbxw-1, Cul1, CK1epsilon, CK1delta, and gamma-catenin. In particular, a previously unrecognized activator, LRRFIP2 (leucine-rich repeat in Flightless interaction protein 2), was found that interacts with Dvl to increase the cellular levels of beta-catenin and activate beta-catenin/LEF/TCF-dependent transcriptional activity. The function of LRRFIP2 is blocked when a dominant negative Dvl (Xdd1) is coexpressed. Expression of LRRFIP2 in Xenopus embryos induced double axis formation and Wnt target gene expression; a dominant negative form of LRRFIP2 suppresses ectopic Wnt signaling in Xenopus embryos and partially inhibits endogenous dorsal axis formation. These data suggest that LRRFIP2 plays an important role in transducing Wnt signals. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 6 |
| Volume Number | 102 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2005-02-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Adenovirus E3 Proteins Metabolism Carrier Proteins Gene Expression Profiling Genome, Human Intercellular Signaling Peptides And Proteins Repetitive Sequences, Amino Acid Signal Transduction Physiology Adaptor Proteins, Signal Transducing Genetics Animals Body Patterning Cells, Cultured Gene Expression Regulation, Developmental Genes, Reporter Oligonucleotide Array Sequence Analysis Phosphoproteins Protein Isoforms Wnt Proteins Xenopus Proteins Xenopus Laevis Embryology Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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