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Wnt/Wingless Signaling Pathway (wingless + signaling_pathway)

Distribution by Scientific Domains

Medical Sciences	50%
Life Sciences	50%

Selected Abstracts

Shaggy/GSK-3, kinase localizes to the centrosome and to specialized cytoskeletal structures in Drosophila

CYTOSKELETON, Issue 6 2006
Yves Bobinnec
Abstract The assembly of a functional bipolar mitotic spindle requires an exquisite regulation of microtubule behavior in time and space. To characterize new elements of this machinery we carried out a GFP based "protein trap" screen and selected fusion proteins which localized to the spindle apparatus. By this method we identified Shaggy, the Drosophila homologue of glycogen synthase kinase-3, (GSK-3,), as a component of centrosomes. GSK-3, acting in the Wingless signaling pathway is involved in a vast range of developmental processes, from pattern formation to cell-fate specification, and is a key factor for cell proliferation in most animals. We exploited our Shaggy::GFP Drosophila line to analyze the subcellular localizations of GSK-3,/Shaggy and shed light on its multiple roles during embryogenesis. We found that Shaggy becomes enriched transiently in a variety of specialized cytoskeletal structures of the embryo, including centrosomes throughout mitosis, suggesting that this kinase is involved in the regulation of many aspects of the cytoskeleton function. Cell Motil. Cytoskeleton 2006. © 2006 Wiley-Liss, Inc. [source]

Cell adhesion system and human cancer morphogenesis

CANCER SCIENCE, Issue 7 2003
Setsuo Hirohashi
Cell-cell adhesion determines the polarity of cells and participates in the maintenance of the cell societies called tissues. Cell-cell adhesiveness is generally reduced in human cancers. Reduced intercellular adhesiveness allows cancer cells to disobey the social order, resulting in destruction of histological structure, which is the morphological hallmark of malignant tumors. Reduced intercellular adhesiveness is also indispensable for cancer invasion and metastasis. A tumor-suppressor gene product, E-cadherin, and its undercoat proteins, catenins, which connect cadherins to actin filaments, are located at lateral borders, concentrating on adherens junctions, of epithelial cells and establish firm cell-cell adhesion. The E-cadherin cell adhesion system in cancer cells is inactivated by various mechanisms that reflect the morphological and biological characteristics of the tumor. Silencing of the E-cadherin gene by DNA hypermethylation around the promoter region occurs frequently, even in precancerous conditions. In diffuse infiltrating cancers, mutations are found in the genes for E-cadherin and ,-and ,-catenins. At the invading front of cancers, the E-cadherin cell adhesion system is inactivated by tyrosine phosphorylation of ,-catenin; an oncogene product, c- erb B-2 protein, is found to associate directly with ,-catenin. The E-cadherin cell adhesion system cross-talks with the Wingless/Wnt signaling pathway through ,-catenin, and expression of genes, which participate in cancer morphogenesis, may be regulated in conjunction with the Wingless/Wnt signaling pathway. Dysadherin, a newly identified cancer-associated cell membrane glycoprotein, down-regulates E-cadherin and promotes cancer metastasis. In conclusion, inactivation of the E-cadherin cell adhesion system by both genetic and epigenetic mechanisms plays a significant role during multistage human carcinogenesis. [source]

Involvement of canonical Wnt/Wingless signaling in the determination of the positional values within the leg segment of the cricket Gryllus bimaculatus

DEVELOPMENT GROWTH & DIFFERENTIATION, Issue 2 2007
Taro Nakamura
The cricket Gryllus bimaculatus is a hemimetabolous insect whose nymphs posses the ability to regenerate amputated legs. Previously, we showed that Gryllus orthologues of Drosophila hedgehog (Gb'hh), wingless (Gb'wg) and decapentaplegic (Gb'dpp) are expressed during leg regeneration and play essential roles in the establishment of the proximal-distal axis. Here, we examined their roles during intercalary regeneration: when a distally amputated tibia with disparate positional values is placed next to a proximally amputated host, intercalary growth occurs in order to regenerate the missing part. In this process, we examined expression patterns of Gb'hh and Gb'wg. We found that expressions of Gb'hh and Gb'wg were induced in a regenerate and the host proximal to the amputated region, but not in the grafted donor distal to the regenerate. This directional induction occurs even in the reversed intercalation. Because these results are consistent with a distal-to-proximal respecification of the regenerate, Gb'wg may be involved in the re-establishment of the positional values in the regenerate. Furthermore, we found that no regeneration occurs when Gb'armadillo (the orthologue of beta-catenin) was knocked down by RNA interference. These results indicate that the canonical Wnt/Wingless signaling pathway is involved in the process of leg regeneration and determination of positional information in the leg segment. [source]

,-Catenin expression in human neural cell lines following exposure to cytokines and growth factors

NEUROPATHOLOGY, Issue 2 2000
Jun-ichi Satoh
,-Catenin acts as a key mediator of the Wnt/Wingless signaling pathway involved in cell proliferation, differentiation and survival. Recent studies have shown that an unstable interaction between ,-catenin and the mutant presenilin-1 induces neuronal apoptosis, and that ,-catenin levels are decreased in the brains of patients with Alzheimer's disease (AD). Since activated microglia and astrocytes play a role in the process of neuronal degeneration in AD, the cytokine/growth factor-regulated expression of ,-catenin in human neural cell lines, including NTera2 teratocarcinoma-derived differentiated neurons (NTera2-N), IMR-32 neuroblastoma, SKN-SH neuroblastoma and U-373MG astrocytoma, was studied quantitatively following exposure to epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), brain-derived neurotrophic factor (BDNF), tumor necrosis factor-, (TNF-,), interleukin (IL)-1,, IL-6, interferon (IFN)-,, transforming growth factor (TGF)-,1, dibutyryl cyclic adenosine 3,,5,-cyclic monophosphate (cAMP) (dbcAMP) or phorbol 12-myristate 13-acetate (PMA). ,-Catenin mRNA expressed constitutively in all of these cell lines was unaffected by treatment with any factors examined. In contrast, ,-catenin protein levels were reduced markedly in NTera2-N cells by exposure to dbcAMP, EGF or bFGF, and in U-373MG cells by treatment with dbcAMP or PMA, but were unaffected in any cell lines by BDNF, TNF-,, IL-1,, IL-6, IFN-, or TGF-,1. These results indicate that ,-catenin is expressed constitutively in human neural cells and downregulated at a protein level by a set of growth factors in a cell type-specific manner. [source]