The Dishevelled, Frizzled approach to Wnt antibody research

The Wnt proteins are highly conserved molecules that play an essential role in regulating cell-to-cell signaling during embryogenesis. The Wnt signaling and receptor binding pathways are complex and diverse, with a large antibody database dedicated to this area of research.

Much of what we know about Wnt arose through research with Xenopus, C. elegans and Drosophila – Wnt was derived from the Wg “wingless-type” Drosophila mutation and INT, a mammalian homologue. Mutations in the Wnt pathways lead to developmental defects and a number of human diseases, including cancer.

Antibody research has suggested the main Wrt signaling mechanism in humans is the canonical pathway, involving both membrane-bound and soluble receptors and mediators. Signaling is initiated when Wrt proteins bind to LRP or Frizzled receptors on the cell membrane. Via a cytoplasmic relay cascade, beta-catenin enters the nucleus, initiating transactivation of Wnt target genes. So far, at least 19 Wnt ligands are known to exist, ranging from 350 to 400 amino acids in length.

The Frizzled (FRZ) antibody database is extensive, with ten FRZ proteins so far discovered in humans. FRZ receptors range from 537 to 706 amino acids in length, with an intracellular C-terminus and extracellular N-terminus containing a cysteine-rich domain, which is also found in tyrosine kinase receptors such as ROR2.

Following Wnt binding, Frizzled receptors trigger activation of Dishevelled (DSH) proteins, a key component of the Wnt receptor complex. This ultimately alters the level of beta catenin reaching the nucleus. If Wnt binding does not occur, a protein complex consisting of axin, GSK-3 and APC promotes degradation of the beta-catenin signaling molecule. Wnt binding inhibits this complex, allowing beta-catenin to enter the nucleus and interact with TCF/LEF transcription factors, promoting gene expression. FRZ also interacts with the LRP protein, which binds FRZ, axin and Wnt and may act to stabilize the Wnt receptor complex.

We at Novus Biologicals are one of the leading antibody suppliers for Wnt signalling research, with an extensive range of proteins, antibodies and lysates in our antibody catalog.

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