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WNT Signaling

Wnts are a class of evolutionarily-conserved, lipid-modified glycoproteins that play a pivotal role in development and homeostasis through a number of different paracrine and autocrine signal-transduction pathways. During early development, Wnt signaling plays a major role in axon guidance, cell polarity, and body axis specification.

Extracellular Wnts bind a variety of different receptors, and initiate signaling in several distinct pathways. Receptors include seven-pass transmembrane Frizzleds and receptor tyrosine kinases ROR and Ryk.

Wnt signaling pathways can result in changes to gene transcription. For example, in the canonical β-catenin signaling pathway Wnt signaling prevents destruction of the transcriptional regulator β-catenin. Wnt signaling can also prompt morphological changes to cellular structure e.g., the non-canonical planar cell polarity pathway induces a kinase cascade that results in reorganization of actin, a core component of the cytoskeleton.

Antagonists

DKK1 (Dickkopf Homolog 1 (Xenopus Laevis)):

This gene encodes a protein that is a member of the dickkopf family. It is a secreted protein with two cysteine rich regions and is involved in embryonic development through its inhibition of the WNT signaling pathway. Elevated levels of DKK1 in bone marrow plasma and peripheral blood is associated with the presence of osteolytic bone lesions in patients with multiple myeloma. [provided by...   More...

beta-Catenin Pathway

APC - Adenomatous Polyposis Coli

This gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. It is also involved in other processes including cell migration and adhesion, transcriptional activation, and apoptosis. Defects in this gene cause familial adenomatous polyposis (FAP), an autosomal dominant pre-malignant disease that usually progresses to malignancy. Disease-associated...   More...

CSNK1A1 (Casein Kinase 1, alpha 1):

Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. It can phosphorylate a large number of proteins. Participates in Wnt signaling. Phosphorylates CTNNB1 at 'Ser-45'. May play a role in segregating chromosomes during mitosis.   More...

TCF7L1 (Transcription Factor 7-Like 1 (T-Cell Specific, HMG-Box)):

This gene encodes a member of the T cell factor/lymphoid enhancer factor family of transcription factors. These transcription factors are activated by beta catenin, mediate the Wnt signaling pathway and are antagonized by the transforming growth factor beta signaling pathway. The encoded protein contains a high mobility group-box DNA binding domain and participates in the regulation of cell...   More...

TCF7L2 (Transcription Factor 7-Like 2 (T-Cell Specific, HMG-Box)):

This gene encodes a high mobility group (HMG) box-containing transcription factor that plays a key role in the Wnt signaling pathway. The protein has been implicated in blood glucose homeostasis. Genetic variants of this gene are associated with increased risk of type 2 diabetes. Several transcript variants encoding multiple different isoforms have been found for this gene.[provided by RefSeq,...   More...

LLGL1 (Lethal Giant Larvae Homolog 1 (Drosophila)):

LLGL2 (Lethal Giant Larvae Homolog 2 (Drosophila)):

TCF3 (Transcription Factor 3 (E2A Immunoglobulin Enhancer Binding Factors E12/E47)):

TCF7 (Transcription Factor 7 (T-Cell Specific, HMG-Box)):

TLE1 (Transducin-Like Enhancer of Split 1 (E(sp1) Homolog, Drosophila)):

TLE2 (Transducin-Like Enhancer of Split 2 (E(sp1) Homolog, Drosophila)):

TLE4 (Transducin-Like Enhancer of Split 4 (E(sp1) Homolog, Drosophila)):

TLE6 (Transducin-Like Enhancer of Split 6 (E(sp1) Homolog, Drosophila)):

Calcium Pathway

CAMK2B (Calcium/calmodulin-Dependent Protein Kinase II beta):

The product of this gene belongs to the serine/threonine protein kinase family and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. Calcium signaling is crucial for several aspects of plasticity at glutamatergic synapses. In mammalian cells, the enzyme is composed of four different chains: alpha, beta, gamma, and delta. The product of this gene is a beta chain. It is possible that...   More...

CAMK2A (Calcium/calmodulin-Dependent Protein Kinase II alpha):

The product of this gene belongs to the serine/threonine protein kinases family, and to the Ca(2+)/calmodulin-dependent protein kinases subfamily. Calcium signaling is crucial for several aspects of plasticity at glutamatergic synapses. This calcium calmodulin-dependent protein kinase is composed of four different chains: alpha, beta, gamma, and delta. The alpha chain encoded by this gene is...   More...

CDC42 (Cell Division Cycle 42 (GTP Binding Protein, 25kDa)):

The protein encoded by this gene is a small GTPase of the Rho-subfamily, which regulates signaling pathways that control diverse cellular functions including cell morphology, migration, endocytosis and cell cycle progression. This protein is highly similar to Saccharomyces cerevisiae Cdc 42, and is able to complement the yeast cdc42-1 mutant. The product of oncogene Dbl was reported to...   More...

PPP3CA (Protein Phosphatase 3, Catalytic Subunit, alpha Isoform):

catalytic subunit of Calcineurin (CaN), ubiquitously expressed Ca2+/CaM-dependent protein phosphatase\; mediates activities of transcription factors and ion channels\; involved in regulation of T-cell activation [RGD, Feb 2006].   More...

PLCB3 (phospholipase C, beta 3 (Phosphatidylinositol-Specific)):

PPP3CB (Protein Phosphatase 3, Catalytic Subunit, beta Isozyme):

PPP3CC (Protein Phosphatase 3, Catalytic Subunit, gamma Isozyme):

Co-Receptors

LRP5 (Low Density Lipoprotein Receptor-Related Protein 5):

This gene encodes a transmembrane low-density lipoprotein receptor that binds and internalizes ligands in the process of receptor-mediated endocytosis. This protein also acts as a co-receptor with Frizzled protein family members for transducing signals by Wnt proteins and was originally cloned on the basis of its association with type 1 diabetes mellitus in humans. This protein plays a key role...   More...

LRP6 (Low Density Lipoprotein Receptor-Related Protein 6):

This gene encodes a member of the low density lipoprotein (LDL) receptor gene family. LDL receptors are transmembrane cell surface proteins involved in receptor-mediated endocytosis of lipoprotein and protein ligands. The protein encoded by this gene functions as a receptor or, with Frizzled, a co-receptor for Wnt and thereby transmits the canonical Wnt/beta-catenin signaling cascade. Through...   More...

Frizzleds

Fzd1 - FZD1

Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK- 3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if...   More...

FZD2 (Frizzled Family Receptor 2):

This intronless gene is a member of the frizzled gene family. Members of this family encode seven-transmembrane domain proteins that are receptors for the wingless type MMTV integration site family of signaling proteins. This gene encodes a protein that is coupled to the beta-catenin canonical signaling pathway. Competition between the wingless-type MMTV integration site family, member 3A and...   More...

LOC100313610 - Frizzled 5/8 Protein Receptor:

FZD7 (Frizzled Family Receptor 7):

PCP Pathway

DAAM1 (Dishevelled Associated Activator of Morphogenesis 1):

Cell motility, adhesion, cytokinesis, and other functions of the cell cortex are mediated by reorganization of the actin cytoskeleton and several formin homology (FH) proteins have been associated with these processes. The protein encoded by this gene contains two FH domains and belongs to a novel FH protein subfamily implicated in cell polarity. A key regulator of cytoskeletal architecture,...   More...

JUN - C-JUN

This gene is the putative transforming gene of avian sarcoma virus 17. It encodes a protein which is highly similar to the viral protein, and which interacts directly with specific target DNA sequences to regulate gene expression. This gene is intronless and is mapped to 1p32-p31, a chromosomal region involved in both translocations and deletions in human malignancies. [provided by RefSeq, Jul...   More...

RHO - Rhodopsin

Retinitis pigmentosa is an inherited progressive disease which is a major cause of blindness in western communities. It can be inherited as an autosomal dominant, autosomal recessive, or X-linked recessive disorder. In the autosomal dominant form,which comprises about 25% of total cases, approximately 30% of families have mutations in the gene encoding the rod photoreceptor-specific protein...   More...

MAPK10 (Mitogen-Activated Protein Kinase 10):

NFAT5 (Nuclear Factor of Activated T-Cells 5, Tonicity-Responsive):

NFATC1 (Nuclear Factor of Activated T-Cells, Cytoplasmic, Calcineurin-Dependent 1):

NFAT1 (Nuclear Factor of Activated T-Cells, Cytoplasmic, Calcineurin-Dependent 2):

NFATC3 (Nuclear Factor of Activated T-Cells, Cytoplasmic, Calcineurin-Dependent 3):

NFATC4 (Nuclear Factor of Activated T-Cells, Cytoplasmic, Calcineurin-Dependent 4):

ROCK1 (rho-Associated, Coiled-Coil Containing Protein Kinase 1):

ROCK2 (rho-Associated, Coiled-Coil Containing Protein Kinase 2):

Receptor Tyrosine Kinases

ROR1 (Receptor Tyrosine Kinase-Like Orphan Receptor 1):

This gene encodes a receptor tyrosine kinase-like orphan receptor that modulates neurite growth in the central nervous system. The encoded protein is a glycosylated type I membrane protein that belongs to the ROR subfamily of cell surface receptors. It is a pseudokinase that lacks catalytic activity and may interact with the non-canonical Wnt signalling pathway. This gene is highly expressed...   More...

ROR2 (Receptor Tyrosine Kinase-Like Orphan Receptor 2):

The protein encoded by this gene is a receptor protein tyrosine kinase and type I transmembrane protein that belongs to the ROR subfamily of cell surface receptors. The protein may be involved in the early formation of the chondrocytes and may be required for cartilage and growth plate development. Mutations in this gene can cause brachydactyly type B, a skeletal disorder characterized by...   More...

RYK (RYK Receptor-Like Tyrosine Kinase):

The protein encoded by this gene is an atypical member of the family of growth factor receptor protein tyrosine kinases, differing from other members at a number of conserved residues in the activation and nucleotide binding domains. This gene product belongs to a subfamily whose members do not appear to be regulated by phosphorylation in the activation segment. It has been suggested that...   More...

WNTs

WNT2 (Wingless-Type MMTV Integration Site Family Member 2):

This gene is a member of the WNT gene family. 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. Alternatively spliced transcript variants have been identified for this gene. [provided...   More...

WNT1 (Wingless-Type MMTV Integration Site Family, Member 1):

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 is very conserved in evolution, and the protein encoded by this gene is known to be...   More...

WNT8B (Wingless-Type MMTV Integration Site Family, Member 8B):

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