Frizzled Family Related Drug Discovery Products
Creative Biolabs has the assays you can rely on for high throughput screening, lead optimization, characterizing and discovering targets, and uncovering the complexity of disease pathways. We can offer membrane protein in vitro assay kits that save valuable laboratory time and is ideal for high throughput screening.
Membrane protein stable cell lines are widely used in many areas of biomedical research. Creative Biolabs can offer membrane protein stable cell lines to stablish in vitro models for High Throughput Screening.
Creative Biolabs' membrane preparations are useful for membrane protein research. We offer membrane preparations to study the role of membrane proteins in diseases. Membrane preparations from Creative Biolabs are quality-assured frozen membranes from cells expressing recombinant or natural receptors.
Creative Biolabs offers high-quality, innovative tools to help research groups accelerate membrane protein drug discovery. They can be found by targets. If there is no product that meets your needs, please contact us.
The primary receptors for the Wnt family of signaling molecules are frizzled proteins, which are present in all animal kingdoms, even the most basic metazoa, but not in plants or simpler (single cell) eukaryotes like yeast. A conserved extracellular cysteine-rich domain (CRD) followed by a domain with seven presumably transmembrane segments characterizes the architecture of frizzled proteins. An abnormal orientation of surface features, such as cuticular bristles and wing hairs, which ordinarily display a precise orientation in relation to the body axis, is known as a tissue polarity phenotype and is caused by loss-of-function mutations in the fz gene. The term "planar cell polarity" (PCP), which is not totally correct, is commonly used to describe this mechanism.
Fig.1. Schematic view of FZDs. (Schulte & Bryja, 2007)
Creative Biolabs provides frizzled family related products to facilitate our customers' development of membrane protein drugs:
Overview of Frizzled Family
Agonist-activated FZDs initiate three major signaling pathways: the FZD/β-catenin pathway, the FZD/Ca2+ pathway, and the FZD/PCP pathway. In the FZD/β-catenin pathway, activation of the phosphoprotein Dishevelled (DVL) results in inhibition of a constitutively active glycogen-synthase kinase 3 within a destructive complex made up of APC and axin, which controls the phosphorylation and cleavage of β-catenin. In the nucleus, the β-catenin that was so spared works with TCF/LEF transcription factors to change the transcription of genes. Information is thought to be transferred from the FZD/PCP route to the small GTPases RHO and RAC and their effectors, primarily ROCK (RHO kinase) and the c-jun-Nterminal kinase-c-jun-AP1 pathway, via DVL. In the FZD/Ca2+ pathway, the agonists cause an increase in intracellular calcium levels in a G-protein-dependent manner, either directly by activating phospholipases or indirectly by causing a decrease in intracellular cyclic GMP, which activates calcium-dependent kinases like Ca2+/calmodulin-dependent protein kinase and PKC. It should be noted that there are still numerous unknowns regarding the primary WNT signaling routes.
Fig.2. Schematic diagram of the Wnt signalling networks. (Jones & Jomary, 2002)
Frizzled Family Drug Discovery
FZD signaling is a constantly evolving subject, therefore fundamental ideas will need to be modified for new models. Future work must focus on developing a thorough pharmacological description of the FZDs that takes into account the specificity of the WNT receptor, dosage impact, receptor-ligand affinities, and in-depth characterization of FZD-G-protein interaction processes. Additionally, the existence of different FZD ligands raises concerns about ligand competition for binding sites, in vivo concentrations of the multiple agonists, and the overall effect of simultaneous stimulation with those ligands.
References
- Schulte, G.; Bryja, V. The Frizzled family of unconventional G-protein-coupled receptors. Trends in pharmacological sciences. 2007, 28(10): 518-525.
- Jones, S. E.; Jomary, C. Secreted Frizzled‐related proteins: searching for relationships and patterns. Bioessays. 2002, 24(9), 811-820.
