Frzb
frizzled-related protein | |||||||
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Identifiers | |||||||
Symbol | FRZB | ||||||
Chr. 2 q31-q33 | |||||||
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Frzb (pronounced like the toy frisbee) is a
Frizzled is a tissue polarity gene in Drosophila melanogaster and encodes integral proteins that function as cell-surface receptors for Wnts called serpentine receptors. The integral membrane proteins contain a cysteine-rich domain thought to be the Wnt binding domain in extracellular region. The signals are initiated at the 7 transmembrane domain and transmitted through receptor coupling to G-proteins.
This protein is expressed in
The serpentine receptors (frzb) couple binds to ligand (Wnt protein) and activates G-proteins. A signal transduction cascade results in the secretion of first and second group antagonists. First group antagonists are composed of secreted Frizzled Related protein family (Sfrp) and Wnt inhibitory factor (Wif). Both Srfp and Wif bind directly to Wnt proteins blocking activation of the receptor. Second group of antagonists contains a class of Wnt inhibitory proteins known as Frizzled Receptor-like Proteins (FRPs). FRPs bind to the LRP (low-density-lipoprotein-related protein) co-receptors blocking activation of the Wnt signaling pathway.
One such pathway that involves Frizzled (Fz) family is the Wnt/
If Wnt is present it binds to Fz-LRP receptors causing axin to bind to intracellular domain of LRP and Fz. Dishevelled (Dvl) is a protein required for Wnt-dependent inhibition complex. The combination of LRP-axin induces Dvl phosphorylation (P) which blocks the APC-axin-GSK3 complex from phosphorylating β-Cat. The accumulated β-Cat then enters the nucleus and converts TCF into a transcriptional activator.
Defects in Frzb are associated with female-specific osteoarthritis (OA) susceptibility which is the most prevalent form of arthritis and common cause of disability.
Frzb (known as Frzb1 or Sfrp3, Secreted Frizzled Related Protein 3) was initially identified as a chondrogenic factor during bone morphogenesis, and was described as a novel marker of the neural crest-derived mesenchymal cells that contribute to dental follicle formation, the future periodontium.[2]
See also
- Signal transduction
- Morphogenesis
- Developmental biology
- Embryogenesis
- Cancer
- Catenin
References
- ^ Ken M. Cadigan and Yan I. Liu (December 2005) “Wnt signaling: complexity at the surface”, Journal of Cell Science 119, 395-402 (http://jcs.biologists.org/cgi/content/full/119/3/395)
- ^ Thimios A. Mitsiadis, Pierfrancesco Pagella and Claudio Cantù. Early Determination of the Periodontal Domain by the Wnt-Antagonist Frzb/Sfrp3. Physiol., 21 November 2017 https://doi.org/10.3389/fphys.2017.00936 [1]
External links
- FRZB+protein at the U.S. National Library of Medicine Medical Subject Headings (MeSH)