The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. It encodes a protein which shows 97%, 85%, and 63% amino acid identity with mouse, chicken, and Xenopus Wnt11 protein, respectively. This gene may play roles in the development of skeleton, kidney and lung, and is considered to be a plausible candidate gene for High Bone Mass Syndrome. [provided by RefSeq, Jul 2008 ...

Recombinant Wnt5b human (Human cells-derived without any tag) 75% Purity provided with 10mg of stabilizer -- AMS.rhW5bL-010-stab -- 10ug

Background: Dysregulation of WNT signaling has been reported in many malignancies. Objective: This study was conducted to investigate the expression pattern of 14 members of the WNT gene family in different immunophenotypic subtypes of ALL. Methods: Semi-quantitative RT-PCR was performed on samples from 71 ALL patients and 36 age-matched healthy individuals. The ALL patients were categorized into BALL (76%), T-ALL (22.6%) and mixed lineage (1.4%) and the B-ALL cases were further classified into pro-B, pre-BI, pre-BII and immature/mature-B based on immunophenotypic results. Results: Among the WNT genes, WNT-7B (p=0.026), WNT-9A (p=0.020) and WNT-16B (p=0.023) were significantly over-expressed, whereas WNT- 2B (p=0.033), WNT-5A (p=0.016), WNT-7A (p|0.0001) and WNT-10A (p|0.0001) were down-regulated in B-ALL. Among the T-ALL subtype, however, significant down-regulation of WNT-2B, WNT-5B, WNT-7A, WNT-10A and WNT-11 was evident. Comparison between B-ALL subtypes showed significant over-expression of WNT-7B,

InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.

An increasing number of studies address the roles of Wnt proteins in shaping leukocyte functions. Recombinant Wnt3a and Wnt5a, prototypical activators of β-Catenin-dependent and -independent Wnt signaling, respectively, are widely used to investigate the effects of Wnt proteins on myeloid cell functions. Recent reports describe both proinflammatory and immunemodulatory effects of Wnt3a and Wnt5a on macrophages, DCs, and microglia. The underlying molecular mechanisms for this divergence are unclear. We show here that recombinant Wnt3a- and Wnt5a-induced cytokine production from murine C57BL/6 macrophages was dependent on TLR4 and inhibited by Polymyxin B. Similarly, impairment of TLR-induced cytokine production upon preexposure to Wnt proteins was TLR4 dependent. The extent of Wnt3a- and Wnt5a-induced inflammatory gene expression greatly varied between Wnt protein lots. We conclude that cytokine responses and TLR tolerization induced by recombinant Wnt proteins are likely explained by ...

Acting as intercellular signals, Wnt proteins regulate the proliferation of cells. Wnt signals are active in numerous contexts, initially in early development and later during the growth and maintenance of various tissues. In comparison to other growth factors, Wnt signals have several unique properties, including a short range of action. Thereby, Wnts predominantly mediate signaling locally, between neighboring cells. In addition, Wnt signals give shape to tissues as cells are proliferating. This is a consequence of the ability of Wnt signaling to confer polarity and asymmetry to cells. Wnt proteins are highly conserved in evolution and are active in every branch of the animal kingdom.. Wnt signaling is often implicated in stem cell control, as a proliferative and self-renewal signal. Mutations in Wnt genes or Wnt pathway components lead to specific developmental defects, while various human diseases, including cancer, are caused by abnormal Wnt signaling. Insights into the mechanisms of Wnt ...

Wnt signalling has important roles during development and in many diseases. As morphogens, hydrophobic Wnt proteins exert their function over a distance to induce patterning and cell differentiation decisions. Recent studies have identified several factors that are required for the secretion of Wnt proteins; however, how Wnts travel in the extracellular space remains a largely unresolved question. Here we show that Wnts are secreted on exosomes both during Drosophila development and in human cells. We demonstrate that exosomes carry Wnts on their surface to induce Wnt signalling activity in target cells. Together with the cargo receptor Evi/WIs, Wnts are transported through endosomal compartments onto exosomes, a process that requires the R-SNARE Ykt6. Our study demonstrates an evolutionarily conserved functional role of extracellular vesicular transport of Wnt proteins ...

Frizzled proteins are seven-transmembrane proteins that act as the primary receptors for Wnt signals. Wnts can bind the the CRD (cysteine-rich domain) of Frizzled. The structure of Wnt as bound to its receptor Frizzled shows that the lipid, sticking out of the Wnt protein, inserts into a hydrophobic cavity in Frizzled (Janda et al, 2012).. LRPs and Arrow in Drosophila are long single-pass transmembrane proteins. Arrow is genetically required for Wingless signaling (Wehrli, 2000) and mouse LRP mutations are similar in phenotype to Wnt mutants (Pinson, 2000).. Beyond the well known receptors Frizzled and LRP, there are several other transmembrane proteins that act as specific receptors for Wnt proteins or the Wnt agonists, such as R-Spondin. In several cases, these receptors play a role in alternative Wnt pathways. See MacDonald and He (2012), Niehrs (2012) and van Amerongen et al (2008) for reviews. R-spondins interact on the cell surface with members of the LGR5 family, to enhance Wnt signaling ...

Wnt signals exercise strong cell-biological and regenerative effects of considerable therapeutic value. There are, however, no specific Wnt agonists and no method for in vivo delivery of purified Wnt proteins. Wnts contain lipid adducts that are required for activity and we exploited this lipophilicity by packaging purified Wnt3a protein into lipid vesicles. Rather than being encapsulated, Wnts are tethered to the liposomal surface, where they enhance and sustain Wnt signaling in vitro. Molecules that effectively antagonize soluble Wnt3a protein but are ineffective against the Wnt3a signal presented by a cell in a paracrine or autocrine manner are also unable to block liposomal Wnt3a activity, suggesting that liposomal packaging mimics the biological state of active Wnts. When delivered subcutaneously, Wnt3a liposomes induce hair follicle neogenesis, demonstrating their robust biological activity in a regenerative context ...

Wnt signal transduction pathway (Wnt STP) is a crucial intracellular pathway mainly due to its participation in important biological processes, functions, and diseases, i.e., embryonic development, stem-cell management, and human cancers among others. This is why Wnt STP is one of the highest researched signal transduction pathways. Study and analysis of its origin, expansion and gradual development to the present state as found in humans is one aspect of Wnt research. The pattern of development and evolution of the Wnt STP among various species is not clear till date. A phylogenetic tree created from Wnt STPs of multiple species may address this issue. In this respect, we construct a phylogenetic tree from modules of Wnt STPs of diverse species. We term it as the Module Tree. A module is nothing but a self-sufficient minimally-dependent subset of the original Wnt STP. Authenticity of the module tree is tested by comparing it with the two reference trees. The module tree performs better than an

In the developing spinal cord, morphogenetic signals secreted from dorsal and ventral signalling centres control dorsoventral (DV) patterning. The Shh/Gli pathway plays a major role in patterning the ventral neural tube but what restricts its activity to specific domains? On p. 237, Alvarez-Medina and colleagues propose that the Wnt canonical pathway fulfils this role. Wnt1 and Wnt3a, which signal through the canonical β-catenin pathway, are expressed in the dorsal midline region of chick embryos. Their misexpression along the DV axis by in ovo electroporation, the authors report, expands dorsal marker gene expression in the developing neural tube, whereas their inhibition suppresses the dorsal programme and expands ventral gene expression. These phenotypes, the authors show, depend on the Wnt-controlled expression of Gli3, which in its repressor form (Gli3R) acts as the main transcriptional repressor of the Shh/Gli pathway. Together, these observations suggest that the Wnt canonical pathway ...

Wnt proteins form a family of highly conserved secreted signaling molecules that regulate cell-to-cell interactions during embryogenesis. Insights into the mechanisms of Wnt action have emerged from several systems: genetics in Drosophila and Caenorhabditis elegans; biochemistry in cell culture and ectopic gene expression in Xenopus embryos. Mutations in Wnt genes or Wnt pathway components lead to specific developmental defects, while various human diseases, including cancer, are caused by abnormal Wnt signaling. As currently understood, Wnt proteins bind to receptors of the Frizzled and LRP families on the cell surface. Through several cytoplasmic relay components, the signal is transduced to beta-catenin, which enters the nucleus and forms a complex with TCF to activate transcription of Wnt target gene (text from [1] ...

The Wnt-beta-catenin signaling pathway has been shown to govern T cell development by regulating the growth and survival of progenitor T cells and immature thymocytes. We explore the role of noncanonical, Wnt-Ca(2+) signaling in fetal T cell development by analyzing mice deficient for Wnt5a. Our findings reveal that Wnt5a produced in the thymic stromal epithelium does not alter the development of progenitor thymocytes, but regulates the survival of alphabeta lineage thymocytes. Loss of Wnt5a down-regulates Bax expression, promotes Bcl-2 expression, and inhibits apoptosis of CD4(+)CD8(+) thymocytes, whereas exogenous Wnt5a increases apoptosis of fetal thymocytes in culture. Furthermore, Wnt5a overexpression increases apoptosis in T cells in vitro and increases protein kinase C (PKC) and calmodulin-dependent kinase II (CamKII) activity while inhibiting beta-catenin expression and activity. Conversely, Wnt5a deficiency results in the inhibition of PKC activation, decreased CamKII activity, and elevation of

Wnt proteins form a family of highly conserved, secreted glycolipoproteins that regulate cell proliferation, cell polarity and cell fate determination during embryonic development and tissue homeostasis. Mutations in Wnt genes or the Wnt signaling pathway components are often linked to human birth defects, cancer and other diseases.. Since the discovery of the Wnt-1 gene 27 years ago, a complex Wnt signaling network with many components having multiple distinct roles and acting in different cellular compartments has been established. The studies of Wnt signaling in human diseases, in stem cell biology and tissue regeneration holds promise for translational medicine.. A few commonly asked questions regarding studies on the Wnt pathways will be touched upon in this blog series:. How to activate the Wnt Signaling Pathway?. 1) Recombinant Wnt Proteins: there are several commercial sources for recombinant Wnt proteins. As most of them are produced in bacteria, endotoxin, purity and active ...

Wnt/β-catenin signaling has been implicated in the terminal asymmetric divisions of neuronal progenitors in vertebrates and invertebrates. However, the role of Wnt ligands in this process remains poorly characterized. Here we used the terminal divisions of the embryonic neuronal progenitors in C. elegans to characterize the role of Wnt ligands during this process focusing on a lineage that produces the cholinergic interneuron AIY. We observed that during interphase the neuronal progenitor is elongated along the anteroposterior axis, then divides along its major axis, generating an anterior and a posterior daughter with different fates. Using time-controlled perturbations, we show that three Wnt ligands, which are transcribed at higher levels at the posterior of the embryo, regulate the orientation of the neuronal progenitor and its asymmetric division. We also identified a role for a Wnt receptor (MOM-5) and a cortical transducer APC (APR-1), which are respectively enriched at the posterior and ...

Wnt inhibitory factor 1 is a protein that in humans is encoded by the WIF1 gene. WIF1 is a lipid-binding protein that binds to Wnt proteins and prevents them from triggering signalling. WNT proteins are extracellular signaling molecules involved in the control of embryonic development. This gene encodes a secreted protein, which binds WNT proteins and inhibits their activities. This protein contains a WNT inhibitory factor (WIF) domain and 5 epidermal growth factor (EGF)-like domains. It may be involved in mesoderm segmentation. This protein is found to be present in fish, amphibia and mammals. GRCh38: Ensembl release 89: ENSG00000156076 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000020218 - Ensembl, May 2017 Human PubMed Reference:. Mouse PubMed Reference:. Entrez Gene: WIF1 WNT inhibitory factor 1. Malinauskas T, Aricescu AR, Lu W, Siebold C, Jones EY (July 2011). Modular mechanism of Wnt signaling inhibition by Wnt inhibitory factor 1. Nature Structural & Molecular ...

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Data Availability StatementAll relevant data are inside the paper. The necessity for Wnt signalling in haemovascular advancement in vertebrates is certainly complicated, with activation from the Wnt pathway with the capacity of both marketing and of inhibiting haematopoiesis. Early research demonstrated that overexpression of -catenin elevated proliferation of haematopoietic stem cells (HSCs), whereas usage of Wnt inhibitors avoided HSC development and decreased their capability to reconstitute the haematopoietic program when transplanted into irradiated mice [1]. Subsequently, conditional appearance of constitutively energetic analyses of mouse HSCs with different hypomorphic mutations in present these cells possess increased Wnt amounts, increased prices of differentiation, and decreased proliferation [4]. Equivalent results were attained in mice, where HSCs had been significantly fewer in number, with poor self-renewal and repopulation potential [5]. In contrast, the non-canonical Wnt ligand ...

Complete information for WNT2 gene (Protein Coding), Wnt Family Member 2, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium

Complete information for WNT16 gene (Protein Coding), Wnt Family Member 16, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium

The recent determination of the Wnt8-Fz8 structure has created new opportunities to better understand the mechanisms by which Wnt proteins activate downstream signaling pathways and has further clarified why lipid modification of Wnt is required for activation.

The secreted Wnt signaling molecules are essential to the coordination of cell-fate decision making in multicellular organisms. In adult animals, the secreted Wnt proteins are critical for tissue regeneration and frequently contribute to cancer. Small molecules that disable the Wnt acyltransferase P …

In the current study, we have shown that human mammary carcinoma is strongly associated with overexpression of the WNT family ligand WNT7B in the tumor stroma and that isolated human breast carcinoma TAMs express WNT7B. Using experimental mice, we have also shown that WNT7b has a key role in malignant progression of the MMTV-PyMT model of luminal breast cancer because it regulates the angiogenic switch, tumor progression, tumor growth, tumor cell invasion, and metastasis. Using conditional inactivation of the Wnt7b gene with the myeloid-restricted Csf1r-icre driver (28), we show that a critical source of Wnt7b is the TAM.. These data are consistent with prior work showing that TAMs can promote angiogenic switching (34) and that WNT7b can regulate angiogenesis and vascular remodeling in other settings, including the developing neuroepithelium (26), the lung (33), and via macrophages, in the eye (25). TAMs in the PyMT model express TIE2 (Supplementary Fig. S1D-S1I) and it has also been shown that ...

Description: The series of molecular signals initiated by binding of a Wnt protein to a frizzled family receptor on the surface of the target cell, followed by propagation of the signal via beta-catenin, and ending with a change in transcription of target genes that contributes to modulating the rate or frequency of cell proliferation.. ...

The Wnt signaling pathway is a conserved pathway. The Wnt family of signaling proteins participates in multiple developmental events during embryogenesis ..

Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule which affects the development of discrete regions of tissues. Is likely to signal over only few cell diameters.

The WNT gene family consists of structurally related genes which encode secreted sigling proteins. These proteins have been implicated in oncogenesis…

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During Xenopus laevis gastrulation, convergent extension is required for the mesoderm to extend into the embryo and shape the embryonic body plan. Recent results from our lab suggest that the inhibition of aquaporin3b (aqp3b) prevents convergent extension of the mesoderm and that aqp3b acts through noncanonical Wnt signaling. Wnt signaling is a key signaling pathway for embryo and tissue development. There are two types of Wnt signaling pathways, the canonical and the noncanonical pathways. There are three separate branches to noncanonical Wnt signaling. Our lab has shown that aqp3b acts through the noncanonical Wnt/Ca2+ pathway and that it acts upstream of the cytoplasmic Wnt signaling pathway member Disheveled (Dsh). The Frizzled7 (fzd7) membrane receptor is part of the noncanonical Wnt/Ca2+ pathway and also acts upstream of Disheveled (Dsh). I will test, whether in this signaling cascade, aqp3b acts upstream or downstream of fzd7. Thus, I will test whether fzd7 activates aqp3b, if aqp3b ...

TY - JOUR. T1 - Wnt4 expression in the differentiating gonad of the frog Rana rugosa. AU - Oshima, Yuki. AU - Hayashi, Toshiyuki. AU - Tokunaga, Shuichi. AU - Nakamura, Masahisa. PY - 2005/6. Y1 - 2005/6. N2 - Wnt4, a member of the Wnt family, is known to influence the sex-determination cascade. In mice having a targeted deletion of Wnt4, masculinization occurs in XX pups. Therefore, in addition to Sry, Wnt4 is also involved in sex determination in mice. In humans, a chromosomal duplication of the WNT4 causes feminization of XY-individuals. Thus, for better understanding of the mechanism of sex determination in vertebrates, it is necessary to examine the expression of Wnt4 at early gonadal development stages in non-mammalians. We first isolated the Wnt4 cDNA from the tetsis of the frog Rana rugosa. R. rugosa Wnt4 had a high similarity (,86%) at the amino acid level with zebra fish, chicken, mouse, and human Wnt4s. We next employed RT-PCR analysis to examine whether Wnt4 was expressed in a ...

WNT5B glycoprotein belongs to the Wnt protein family. Limited investigations revealed a possible role of WNT5B in malignancies, such as triple-negative breast cancer and oral squamous cell carcinoma. However, whether WNT5B contributes to the progression of lung adenocarcinoma (LAD) remains unclear. Here, we initially determine that WNT5B is highly expressed in LAD and is positively correlated with lymph node metastasis and TNM stage. Consistently, clinical analysis reveals WNT5B as an independent prognostic biomarker in LAD. Silencing WNT5B suppresses the proliferation of LAD both in vitro and in vivo by interfering G1/S cell-cycle progression and modulating amino acid metabolism, revealing its remarkable oncogenic role in LAD. Of note, we also identified miR-5587-3p as a negative upstream regulator of WNT5B in LAD, which may help develop therapies targeting LAD patients with high WNT5B expression. Taken together, our results revealed an oncogenic role of WNT5B in LAD, which could be a prognostic

Author(s): Aznar, Nicolas; Sun, Nina; Dunkel, Ying; Ear, Jason; Buschman, Matthew D; Ghosh, Pradipta | Abstract: Cellular proliferation is antagonistically regulated by canonical and noncanonical Wnt signals; their dysbalance triggers cancers. We previously showed that a multimodular signal transducer, Daple, enhances PI3-K→Akt signals within the noncanonical Wnt signaling pathway and antagonistically inhibits canonical Wnt responses. Here we demonstrate that the PI3-K→Akt pathway serves as a positive feedback loop that further enhances noncanonical Wnt signals by compartmentalizing β-catenin. By phosphorylating the phosphoinositide- (PI) binding domain of Daple, Akt abolishes Daples ability to bind PI3-P-enriched endosomes that engage dynein motor complex for long-distance trafficking of β-catenin/E-cadherin complexes to pericentriolar recycling endosomes (PCREs). Phosphorylation compartmentalizes Daple/β-catenin/E-cadherin complexes to cell-cell contact sites, enhances noncanonical Wnt signals

Results qPCR analysis showed increased expression of the alarmins S100A8/A9 and several members of the canonical Wnt signaling pathway in the CIOA model at all time points measured. In the DMM model, the expression of S100A8/A9 and Wnt16 and WISP1 was mainly increased at day 28 after induction. Kinetics of S100 and Wnt expression were comparable, as was observed in both models. This gave rise to the question if an interrelationship existed between these factors. Therefore, we overexpressed Wnt8a and Wnt16, two canonical Wnts, with the use of adenoviral vectors. However, this did not result in increased expression of S100A8 and S100A9, both on RNA and protein level. In contrast, we found that injection of S100A8 increased the expression of Wnt16 in the synovium and accumulation of β-catenin, a hallmark of canonical Wnt signaling, in both cartilage and synovium. In addition, the downstream mediator of canonical Wnt signaling WISP1, was increased. Furthermore, we found reduced β-catenin ...

Limb-Bud and Heart (LBH) is a novel key transcriptional regulator of vertebrate development. However, the molecular mechanisms upstream of LBH and its role in adult development are unknown. Here we show that in epithelial development, LBH expression is tightly controlled by Wnt signaling. LBH is transcriptionally induced by the canonical Wnt pathway, as evident by the presence of functional TCF/LEF binding sites in the LBH locus and rapid beta-catenin-dependent upregulation of endogenous LBH by Wnt3a. In contrast, LBH induction by Wnt/beta-catenin signaling is inhibited by Wnt7a, which in limb development signals through a non-canonical pathway involving Lmx1b. Furthermore, we show that Lbh is aberrantly overexpressed in mammary tumors of MMTV-Wnt1 transgenic mice and in aggressive basal-subtype human breast cancers that display Wnt/beta-catenin hyperactivation. Deregulation of LBH in human breast cancer appears to be Wnt/beta-catenin dependent as DKK1 and Wnt7a inhibit LBH expression in breast

Wnt signaling plays a central role in development, adult tissue homeostasis, and cancer. Several steps in the canonical Wnt/β-catenin signaling cascade are regulated by ubiquitylation, a protein modification that influences the stability, subcellular localization, or interactions of target proteins. To identify regulators of the Wnt/β-catenin pathway, we performed an RNA interference screen in Caenorhabditis elegans and identified the HECT domain-containing ubiquitin ligase EEL-1 as an inhibitor of Wnt signaling. In human embryonic kidney 293T cells, knockdown of the EEL-1 homolog Huwe1 enhanced the activity of a Wnt reporter in cells stimulated with Wnt3a or in cells that overexpressed casein kinase 1 (CK1) or a constitutively active mutant of the Wnt co-receptor low-density lipoprotein receptor-related protein 6 (LRP6). However, knockdown of Huwe1 had no effect on reporter gene expression in cells expressing constitutively active β-catenin, suggesting that Huwe1 inhibited Wnt signaling ...

Wnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, in many different species and organs. There are at least three different Wnt pathways: the canonical pathway, the planar cell polarity (PCP) pathway and the Wnt/Ca2+ pathway. In the canonical Wnt pathway, the major effect of Wnt ligand binding to its receptor is the stabilization of cytoplasmic beta-catenin through inhibition of the bea-catenin degradation complex. Beta-catenin is then free to enter the nucleus and activate Wnt-regulated genes through its interaction with TCF (T-cell factor) family transcription factors and concomitant recruitment of coactivators. Planar cell polarity (PCP) signaling leads to the activation of the small GTPases RHOA (RAS homologue gene-family member A) and RAC1, which activate the stress kinase JNK (Jun N-terminal kinase) and ROCK (RHO-associated ...

Wnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, in many different species and organs. There are at least three different Wnt pathways: the canonical pathway, the planar cell polarity (PCP) pathway and the Wnt/Ca2+ pathway. In the canonical Wnt pathway, the major effect of Wnt ligand binding to its receptor is the stabilization of cytoplasmic beta-catenin through inhibition of the bea-catenin degradation complex. Beta-catenin is then free to enter the nucleus and activate Wnt-regulated genes through its interaction with TCF (T-cell factor) family transcription factors and concomitant recruitment of coactivators. Planar cell polarity (PCP) signaling leads to the activation of the small GTPases RHOA (RAS homologue gene-family member A) and RAC1, which activate the stress kinase JNK (Jun N-terminal kinase) and ROCK (RHO-associated ...

Background Signaling by the Wnt family of secreted glycoproteins through their receptors, the frizzled (Fz) family of seven-pass transmembrane proteins, is critical for numerous cell fate and tissue polarity decisions during development. murine pancreatic insulin-cell migration. Conclusion Our results implicate a conserved role of a Wnt5/Fz2 signaling pathway in islet formation during pancreatic development. This study opens the door for further investigation into a role of Wnt signaling in vertebrate organ development and disease. Background Wnt signaling pathways play important Klf4 functions in both normal development and in the pathogenesis of a variety of diseases, including cancer [1]. Activation of a Wnt signaling pathway requires conversation between a secreted glycoprotein, Wnt, and a seven-pass transmembrane receptor protein, Frizzled (Fz). Different combinations of Wnt and Fz ligand-receptor pairs can transduce at least three distinct kinds of intracellular signaling pathways. The ...

Wnt signaling is mediated through 1) the beta-catenin dependent canonical pathway and, 2) the beta-catenin independent pathways. Multiple receptors, including Fzds, Lrps, Ror2 and Ryk, are involved in Wnt signaling. Ror2 is a single-span transmembrane receptor-tyrosine kinase (RTK). The functions of Ror2 in mediating the non-canonical Wnt signaling have been well established. The role of Ror2 in canonical Wnt signaling is not fully understood. Here we report that Ror2 also positively modulates Wnt3a-activated canonical signaling in a lung carcinoma, H441 cell line. This activity of Ror2 is dependent on cooperative interactions with Fzd2 but not Fzd7. In addition, Ror2-mediated enhancement of canonical signaling requires the extracellular CRD, but not the intracellular PRD domain of Ror2. We further provide evidence that the positive effect of Ror2 on canonical Wnt signaling is inhibited by Dkk1 and Krm1 suggesting that Ror2 enhances an Lrp-dependent STF response. The current study demonstrates the

Intestinal intraepithelial lymphocytes that reside within the epithelium of the intestine form one of the main branches of the immune system. A majority of IELs express CD8α homodimer together with other molecules associated with immune regulation. Growing evidence points to the WNT signaling pathway as a pivotal piece in the immune balance and focuses on its direct regulation in intestinal epithelium. Therefore we decided to investigate its role in IELs immune status determination. DSS colitis was induced in male C57BL mice. IELs were isolated from colon samples using mechanical dissociation followed by percoll gradient purification and Magnetic-activated cell sorting. Phenotype and cytokine production and condition with Wnts were analyzed by flow cytometry, real-time PCR or ELISA. Proliferation of lymphocytes were evaluated using CFSE dilution. Cell responses after WNT pathway interference were also evaluated. Non-canonical WNT pathway elements represented by FZD5, WNT5A and NFATc1 were remarkably

Wnt11, a member of the evolutionarily conserved Wnt family of glycoproteins, plays important roles in cellular migration, proliferation, and differentiation during embryogenesis. Although Wnt11 induces cardiac differentiation in bone marrow cells, the underlying molecular mechanisms remain unclear. We hypothesized that Wnt11-induced cardiac differentiation of mesenchymal stem cells (MSCs) involves calcium-calmodulin dependent kinase II (CamKII), which is activated via the noncanonical Wnt-Calcium pathway. Murine MSCs were isolated by adhesion to plastic and propagated in culture. For Wnt11 exposure, MSCs were cultured on the bottom of plates with Wnt11-secreting 293 cells on inserts. Empty vector-bearing 293 cells served as controls. Exposure to Wnt11 increased the levels of both phosphorylated (activated) CamKII and p-STAT3 in MSCs (Fig. 1A). The addition of CamKII-bearing plasmids to culture increased p-STAT3 levels in MSCs in a dose-dependent fashion, indicating that CamKII can induce robust ...

Introduction: We have previously shown that in vivo administration of Sfrp2, an inhibitor of canonical Wnt signaling, into injured myocardium enhanced cardiac regeneration. In vitro, Sfrp2 selectively bound to Wnt6 expressed in cardiac progenitor cells (CPCs) and induced cell cycle arrest and cardiac differentiation. Here, we explore the role of Wnt6 inhibition by Sfrp2 in modulating Wnt pathways and regulation of CPC proliferation and differentiation. We also employ lineage tracing to investigate the contribution of CPCs to the in vivo effects of Sfrp2.. Methods: Sca1+ CPCs were established and treated with recombinant Sfrp2 or Wnt6. Wnt pathway activation was measured by Western blotting. Proliferation was assessed by BrdU. Differentiation was documented by Nkx2.5 and Gata4 staining. Recombinant Sfrp2 protein was injected in Sca1-eGFP mice after ischemia/reperfusion injury. Co-staining of GFP with cardiac markers was assessed by confocal microscopy. Cardiac function was evaluated by ...

Proto-oncogene protein Wnt-1 is a protein that in humans is encoded by the WNT1 gene. The WNT gene family consists of structurally related genes that encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. It is very conserved in evolution, and the protein encoded by this gene is known to be 98% identical to the mouse Wnt1 protein at the amino acid level. The studies in mouse indicate that the Wnt1 protein functions in the induction of the mesencephalon and cerebellum. This gene was originally considered as a candidate gene for Joubert syndrome, an autosomal recessive disorder with cerebellar hypoplasia as a leading feature. However, further studies suggested that the gene mutations might not have a significant role in Joubert syndrome. This gene is clustered with another family member, WNT10B, in the ...

We have developed selectively replicating adenoviruses capable of targeting cells with activation of the wnt pathway. These viruses could potentially be used for treatment of liver metastases from colorectal tumors. Since the Tcf-E2 and Tcf-E1B promoters are not activated to wild-type levels in some colon cancer cell lines (Fig.6B), the Tcf viruses are likely to replicate poorly in some colon tumors in vivo, despite the near universality of wnt pathway activation in colon cancer. The reason for the failure of activation of the viral Tcf promoters in some colon cell lines is unknown. Globally reduced activation of the wnt pathway is one possibility. If that is the explanation, it should be possible to develop a clinical test to identify susceptible tumors, perhaps based on microarray analysis or immunohistochemical staining for overexpression of β-catenin or wnt target genes. Such a test would also permit use of the viruses to treat tumor types in which wnt pathway activation is less frequent ...

The canonical Wnt/β-catenin signalling pathway governs diverse developmental, homeostatic and pathological processes. Palmitoylated Wnt ligands engage cell-surface frizzled (FZD) receptors and LRP5 and LRP6 co-receptors, enabling β-catenin nuclear translocation and TCF/LEF-dependent gene transactivation. Mutations in Wnt downstream signalling components have revealed diverse functions thought to be carried out by Wnt ligands themselves. However, redundancy between the 19 mammalian Wnt proteins and 10 FZD receptors and Wnt hydrophobicity have made it difficult to attribute these functions directly to Wnt ligands. For example, individual mutations in Wnt ligands have not revealed homeostatic phenotypes in the intestinal epithelium-an archetypal canonical, Wnt pathway-dependent, rapidly self-renewing tissue, the regeneration of which is fueled by proliferative crypt Lgr5(+) intestinal stem cells (ISCs). R-spondin ligands (RSPO1-RSPO4) engage distinct LGR4-LGR6, RNF43 and ZNRF3 receptor classes, ...

Mest (mesoderm-specific transcript)/Peg1 (paternally expressed gene 1) is an imprinted gene that plays important roles in embryo development, although its biochemical role has not been determined. Ectopic expression of Mest/Peg1 inhibited Wnt-mediated reporter activity by enhancing the ubiquitination of β-catenin. The maturation and plasma membrane localization of the Wnt co-receptor LRP6 [LDLR (low-density lipoprotein receptor)-related protein 6], which are both necessary for Wnt signalling, were blocked by the expression of Mest/Peg1. Mest/Peg1 inhibited maturation of LRP6 by controlling the glycosylation of LRP6. Knockdown of Mest/Peg1, which might enhance Wnt signalling, blocked adipogenic differentiation of 3T3-L1 cells. Overall, our results suggest that Mest/Peg1 is a novel regulator of Wnt/β-catenin signalling during adipogenic differentiation. ...

Wnt genes belong to a multigene family encoding secreted proteins that activate receptor-mediated signal transduction pathways involved in both development and disease. The best-understood Wnt pathway is the Wnt/β-catenin pathway. In this pathway, the Wnt signal leads to activation of the nuclear functions of β-catenin, which in turn activates gene expression leading to cell survival, proliferation, or differentiation. A second vertebrate Wnt pathway, the Wnt/Ca2+ pathway, promotes intracellular Ca2+ release and regulates cell movements in development and in some cancers. We have three goals in studying Wnts. Our first goal is to understand the normal functions of Wnt pathways in vertebrates, focusing on regeneration and response to injury. Our second goal is to understand the biochemistry of a Wnt signal. Our third goal is to leverage this understanding of the normal biology of Wnts to determine whether Wnt signaling is involved in various injuries and diseases and, if it is, to make ...

Some tumors are composed of heterogeneous cells, and an emerging concept is that a subset of these cells are cancer stem cells, which can undergo proliferation and self-renewal or can differentiate and contribute to the mass of the tumor (see Korkaya and Wicha). Noting that colon carcinomas, which have mutations that should increase Wnt signaling (APC mutations), exhibit heterogeneity in the abundance of nuclear β-catenin (the effector of Wnt signaling), Vermeulen et al. expressed a Wnt reporter gene (TOP-GFP) in cultured patient colon cancer cells that were positive for markers of cancer stem cells to explore how Wnt signaling heterogeneity affected tumorigenic potential and the maintenance of stemness. Clones from single cells exhibited a large variation in β-catenin nuclear localization and in green fluorescent protein (GFP) intensity, which allowed the authors to divide the cells into high (TOP-GFPhigh), intermediate (TOP-GFPintermediate), and low (TOP-GFPlow) populations. Microarray ...

Yes‑associated protein (YAP) acts as a transcriptional co‑activator in gene expression and cell proliferation control by binding to the transcriptional factor TEA domain (TEAD) of the Hippo signaling pathway in the nucleus, and also acts as a regulator by binding to another transcriptional co‑activator, β‑catenin of the Wnt signaling pathway. Whether YAP preferentially acts as a transcriptional co‑regulator of the activity of the Hippo signaling pathway or as a regulator in the Wnt signaling pathway depends on the cell type. Nuclear YAP upregulates the expression of β‑catenin, while cytoplasmic YAP has a negative effect on this expression. The present mini‑review focused on the important roles of YAP and further discussed the cross‑links between the Wnt and Hippo signaling pathways. The Wnt and Hippo signaling pathways are both related to the development of fibrosis or cancer. The current review discussed treatment approaches for these conditions based on the two pathways. YAP, ...

Aberrant epithelial repair responses to cigarette smoke contribute to airway remodeling in COPD, a chronic inflammatory respiratory disease. The WNT pathway is re-activated upon inflammation, tissue injury and repair in multiple organs, including the lung, but its role in COPD is unknown. We aimed to investigate whether dysregulated expression of WNT genes may contribute to airway remodeling in COPD.. We studied expression of various WNT ligands, WNT receptors and WNT target/remodeling genes (e.g. fibronectin, periostin, MMP-2 and MMP-9) in the presence and absence of cigarette smoke extract (CSE) in primary bronchial epithelial cells (PBECs) from COPD patients and (non-)smoking controls and/or human bronchial epithelial BEAS-2B cells (qPCR, immunodetection). Additionally, we studied mRNA expression of WNT genes in lung homogenates from Balb/c mice upon 5 days of smoking.. CSE induced a significant increase in the mRNA expression of WNT-5A and WNT-5B, but not of the other detected WNT ligands ...

As mentioned above, there is little evidence that active canonical Wnt signaling occurs in the primary developing or adult myocardium. This view is based primarily on studies that have used the TOPGAL and BAT-GAL reporter mice, and it contrasts with several reports of Wnt ligand expression being present in the adult mammalian heart(Garriock et al., 2005; Jaspard et al., 2000; Monkley et al., 1996; Zakin et al., 1998). Other studies have suggested an important role for β-catenin and Gsk3β in postnatal myocardial growth (Hardt and Sadoshima, 2002; Masuelli et al., 2003; Tseng et al.,2006). These studies have, for the most part, not invoked a Wnt ligand and are based on the role of Gsk3β in stabilizing β-catenin,leading to increased LEF/TCF activation. Stabilized β-catenin in isolated cardiac myocytes or in vivo results in increased myocyte growth with or without the presence of hypertrophic stimuli(Haq et al., 2003; Tseng et al., 2006). This stabilization of β-catenin is thought to occur in ...

Our studies are focused on the revelation of WNT5A, a secreted glycoprotein. WNT5A belongs to the non-transforming class of WNTs, and upon binding to different receptors or co-receptor complexes, it elicits non-canonical (ß-catenin-independent) signaling. WNT5A act as both tumor promoter as well as tumor suppressor, depending on cell type. For example, in breast cancer loss of WNT5A protein is associated with poor survival. In contrast, WNT5A expression is associated with increased metastasis and reduced survival in melanoma patients. Our laboratory focusses on how WNT5A expression is regulated in these cancers and deciphering the WNT5A signaling pathways governing cancer cell migration and invasion. On therapeutic front, we have developed a hexapeptide, Foxy5 (an agonist of WNT5A) which is in clinical trial for breast cancer, prostate cancer and colon carcinoma (NCT02020291). Another peptide, Box5 (a WNT5A derived antagonist) is in pre-clinical trials for malignant melanoma ...

The tumor antigen 5T4/WAIF1 (Wnt-activated inhibitory factor 1; also known as Trophoblast glycoprotein TPBG) is a cell surface protein targeted in multiple cancer immunotherapy clinical trials. Recently, it has been shown that 5T4/WAIF1 inhibits Wnt/β-catenin signaling, a signaling system central to many developmental and pathological processes. Wnt/β-catenin signaling is controlled by multiple inhibitors and activators. Here, we report crystal structures for the extracellular domain of 5T4/WAIF1 at 1.8 Å resolution. They reveal a highly glycosylated, rigid core, comprising eight leucine-rich repeats (LRRs), which serves as a platform to present evolutionarily conserved surface residues in the N-terminal LRR1. Structural and cell-based analyses, coupled with previously reported in vivo data, suggest that Tyr325 plus the LRR1 surface centered on a second exposed aromatic residue, Phe97, are essential for inhibition of Wnt/β-catenin signaling. These results provide a structural basis for the

Wnt5a是Wnt家族成员之一[1]，其与肿瘤的关系虽有一些研究，但作用尚不清楚[2]，有报道认为是促癌基因，也有认为是抑癌基因。同样，Wnt5a在乳腺癌中的作用，特别是与乳腺癌发生发展的重要机制上皮间质转化（epithelial mesenchymal ...

Enhanced sensitivity to Wnts is an emerging hallmark of a subset of cancers, defined in part by mutations regulating the abundance of their receptors. Whether these mutations identify a clinical opportunity is an important question. Inhibition of Wnt secretion by blocking an essential post-translational modification, palmitoleation, provides a useful therapeutic intervention. We developed a novel potent, orally available PORCN inhibitor, ETC-1922159 (henceforth called ETC-159) that blocks the secretion and activity of all Wnts. ETC-159 is remarkably effective in treating RSPO-translocation bearing colorectal cancer (CRC) patient-derived xenografts. This is the first example of effective targeted therapy for this subset of CRC. Consistent with a central role of Wnt signaling in regulation of gene expression, inhibition of PORCN in RSPO3-translocated cancers causes a marked remodeling of the transcriptome, with loss of cell cycle, stem cell and proliferation genes, and an increase in ...

Wnt9a - Wnt9a (untagged) - Mouse wingless-type MMTV integration site 9A (cDNA clone MGC:76532 IMAGE:30435371), (10ug) available for purchase from OriGene - Your Gene Company.

Wnt6 - Wnt6 (untagged) - Mouse wingless-related MMTV integration site 6 (cDNA clone MGC:59372 IMAGE:6511061), (10ug) available for purchase from OriGene - Your Gene Company.

Wnt signaling is a fundamental pathway in embryogenesis which is evolutionary conserved from metazoans to humans. Much of our understanding of Wnt signaling events emerged from key developmental studi

Rabbit polyconal antibody raised against synthetic peptide of WNT1. A synthetic peptide corresponding to 19 amino acids at internal region of human WNT1. (PAB28353) - Products - Abnova

Plasmid RCAS (A) Wnt3a (CT#169) from Dr. Cliff Tabins lab contains the insert Wnt3a and is published in Science. 1998 May 22. 280(5367):1274-7. This plasmid is available through Addgene.

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The SFB1324 research program consists of 13 projects and three technology platforms working on two research areas that are of key importance for advancing our understanding of molecular mechanisms governing Wnt signal transduction. In particular, the CRC1324 will focus on two overarching topics:. Research focus A: Wnt secretion, trafficking and receptor-ligand interactions. • How are Wnt proteins produced, how are they modified and how are they transported in the extracellularspace ...

This gene is a member of the WNT gene family, which consists of structurally related genes that encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. Among members of the human WNT family, this gene product is most similar to WNT7A protein. [provided by RefSeq, Oct 2008 ...

Wingless-Type MMTV Integration Site Family, Member 3A Human Recombinant, Protein Wnt-3a, MGC119418, MGC119419, MGC119420, WNT3A, wingless-type MMTV integration site family member 3A.

Progenitors establish a single-cell length WNT morphogen gradient to transmit signals directionally and differentially to neighbors.

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RA downregulates Wnt and promote KA tumour regression.(a) RNA sequencing heatmap showing a subset of genes differentially expressed between tumour in growth (0

This project deciphers the regulatory mechanism underlying the making of Wnt and its signaling effects in signal-producing and signal-receiving cells. The main focus is to test our hypothesis that the newly identified Gpr177/mouse Wntless is a master regulator for intracellular trafficking of Wnt. We currently investigate the reciprocal regulation of Wnt and Gpr177 in craniofacial, skeletal, skin, tooth and mammary development, as well as the Gpr177-mediated regulation of Wnt in birth defects and cancers. ...

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