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Wnt Interactions
Published by Anonymous on 2007/9/30 (2156 reads)
1: Cell Signal. 2007 Apr;19(4):659-71. Epub 2006 Nov 16.

Multiplicity of the interactions of Wnt proteins and their receptors.

Kikuchi A, Yamamoto H, Kishida S.

Department of Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Hiroshima, Japan. akikuchi@hiroshima-u.ac.jp

Wnts are secreted proteins that are essential for a wide array of developmental and physiological processes. They signal across the plasma membranes by interacting with serpentine receptors of the Frizzled (Fz) family and members of the low-density-lipoprotein receptor-related protein (LRP) family. Recent advances in the Wnt signaling field have revealed that Wnt-unrelated proteins activate or suppress Wnt signaling by binding to Fzs or LRP5/6 and that atypical receptor tyrosine kinases mediate Wnt signaling independently of Fz and/or function as a Fz co-receptor. This review highlights recent progress in our understanding of the multiplicity of Wnts and their receptors. We discuss how the interaction between the ligands and receptors activate distinct intracellular signaling pathways. We also discuss how intracellular trafficking of Wnt signaling components can regulate the sensitivity of cells to Wnts.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 17188462 [PubMed - indexed for MEDLINE]


2: Trends Mol Med. 2004 Dec;10(12):577-80.

Unexpected Hedgehog-Wnt interactions in epithelial differentiation.

Watt FM.

Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK. fionna.watt@cancer.org.uk

Wnt and Hedgehog (Hh) signalling regulate stem-cell self-renewal and differentiation in a range of epithelia and the inappropriate activation of these pathways contributes to epithelial cancers. Recently, it was reported that Indian Hedgehog (Ihh) antagonises Wnt signalling in colonic epithelium. This observation contrasts with other reports of positive synergy between the pathways and challenges the view that systemically administered Hedgehog antagonists could be beneficial for the treatment of intestinal tumours. The work is discussed in the broader context of Ihh expression and function in epithelia and the different ways in which the Hh and Wnt pathways interact.

Publication Types:

PMID: 15567325 [PubMed - indexed for MEDLINE]


3: Front Biosci. 2004 May 1;9:1333-8.

Specificity of WNT-receptor interactions.

Hsieh JC.

Department of Biochemistry and Cell Biology, Center for Developmental Genetics, State University of New York at Stony Brook, Stony Brook, New York 11794, USA. jhsieh@ms.cc.sunysb.edu

The highly conserved Wnt signaling proteins play critical roles in guiding pattern formation, cell fate decision, and morphogenetic movement during animal development. They bind to the Frizzled family of seven-pass transmembrane proteins and initiate at least three different intracellular signaling pathways, resulting in regulation of gene expression and/or changes in cell behavior. A single transmembrane protein from the low-density-lipoprotein family functions as a co-receptor in the canonical/beta-catenin pathway. The specificity of Wnt signaling depends in part on the affinities between various Wnt-Frizzled pairs. A Wnt-dependent receptor dimerization or clustering step has been hypothesized as the step that initiates the canonical signaling cascade in cells.

Publication Types:

PMID: 14977548 [PubMed - indexed for MEDLINE]


4: Gastroenterology. 2000 Oct;119(4):1161-4.

Comment on:
Gastroenterology. 2000 Oct;119(4):1045-53.

Touch and go: mediating cell-to-cell interactions and Wnt signaling in gastrointestinal tumor formation.

Groden J.

Publication Types:

PMID: 11040203 [PubMed - indexed for MEDLINE]


5: Biochim Biophys Acta. 2000 Feb 2;1495(2):168-82.

Biochemical interactions in the wnt pathway.

Seidensticker MJ, Behrens J.

Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13122, Berlin, Germany.

The wnt signal transduction pathway is involved in many differentiation events during embryonic development and can lead to tumor formation after aberrant activation of its components. The cytoplasmic component beta-catenin is central to the transmission of wnt signals to the nucleus: in the absence of wnts beta-catenin is constitutively degraded in proteasomes, whereas in the presence of wnts beta-catenin is stabilized and associates with HMG box transcription factors of the LEF/TCF family. In tumors, beta-catenin degradation is blocked by mutations of the tumor suppressor gene APC (adenomatous polyposis coli), or of beta-catenin itself. As a consequence, constitutive TCF/beta-catenin complexes are formed and activate oncogenic target genes. This review discusses the mechanisms that silence the pathway in cells that do not receive a wnt signal and goes on to describe the regulatory steps involved in the activation of the pathway.

Publication Types:

PMID: 10656974 [PubMed - indexed for MEDLINE]

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