Frzb
Encyclopedia
Frzb is a Wnt-binding protein
especially important in embryonic development. It is a competitor for the cell-surface G-protein receptor Frizzled
.
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.
The mammal homolog
to Frizzled is a frizzled-related protein known as frzb. This protein is expressed in chondrocyte
s making it important in skeletal development in the embryo and fetus. Frzb is localized in the extracellular plasma membrane. Unlike frizzled, frzb lacks the 7 transmembrane domains normally found in G-protein-coupled receptors. It is still considered a homolog of frizzled because it contains a Cysteine Rich Domain (CRD), and because of its intracellular C-terminus which is crucial for signaling. The CRD is highly conserved in diverse proteins, such as receptor tyrosine kinases and functions as a ligand binding domain. The C-terminal is a carboxyl terminus located intracellularly and is required for canonical signaling.
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 antagonist
s. 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/β-Catenin (β-Cat) signaling . β-Cat is an intracellular signal that is held in check by axin. In this pathway, the activation of Wnt receptors can be transduced by the canonical pathway via a series of phosphorylation
steps leading to stabilization and nuclear import of β-Cat into the nucleus where β-Cat associates with T-cell factor (TCF), a DNA-binding protein family. The β-Cat and TCF complex activates target genes of the Wnt pathway. In the absence of Wnt, β-Catenin is phosphorylated by complex containing GSK3 (glycogen synthase kinase 3) which targets β-Cat for protesosomal degradation. In the nucleus, members of the T-cell factor (TCF) family of DNA-binding proteins repress Wnt targets along with co-repressors such as Groucho (Gro).
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.
http://jcs.biologists.org/content/vol119/issue3/images/large/JCS02826F1.jpeg
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
especially important in embryonic development. It is a competitor for the cell-surface G-protein receptor Frizzled
Frizzled
Frizzled is a family of G protein-coupled receptor proteins that serve as receptors in the Wnt signaling pathway and other signaling pathways. When activated, Frizzled leads to activation of Dishevelled in the cytosol.-Species distribution:...
.
Frizzled is a tissue polarity gene in Drosophila melanogaster
Drosophila melanogaster
Drosophila melanogaster is a species of Diptera, or the order of flies, in the family Drosophilidae. The species is known generally as the common fruit fly or vinegar fly. Starting from Charles W...
and encodes integral proteins that function as cell-surface receptors for Wnts called serpentine receptors. The integral membrane proteins contain a cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
-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.
The mammal homolog
Homology (biology)
Homology forms the basis of organization for comparative biology. In 1843, Richard Owen defined homology as "the same organ in different animals under every variety of form and function". Organs as different as a bat's wing, a seal's flipper, a cat's paw and a human hand have a common underlying...
to Frizzled is a frizzled-related protein known as frzb. This protein is expressed in chondrocyte
Chondrocyte
Chondrocytes are the only cells found in cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteoglycans...
s making it important in skeletal development in the embryo and fetus. Frzb is localized in the extracellular plasma membrane. Unlike frizzled, frzb lacks the 7 transmembrane domains normally found in G-protein-coupled receptors. It is still considered a homolog of frizzled because it contains a Cysteine Rich Domain (CRD), and because of its intracellular C-terminus which is crucial for signaling. The CRD is highly conserved in diverse proteins, such as receptor tyrosine kinases and functions as a ligand binding domain. The C-terminal is a carboxyl terminus located intracellularly and is required for canonical signaling.
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 antagonist
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
s. 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/β-Catenin (β-Cat) signaling . β-Cat is an intracellular signal that is held in check by axin. In this pathway, the activation of Wnt receptors can be transduced by the canonical pathway via a series of phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
steps leading to stabilization and nuclear import of β-Cat into the nucleus where β-Cat associates with T-cell factor (TCF), a DNA-binding protein family. The β-Cat and TCF complex activates target genes of the Wnt pathway. In the absence of Wnt, β-Catenin is phosphorylated by complex containing GSK3 (glycogen synthase kinase 3) which targets β-Cat for protesosomal degradation. In the nucleus, members of the T-cell factor (TCF) family of DNA-binding proteins repress Wnt targets along with co-repressors such as Groucho (Gro).
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.
http://jcs.biologists.org/content/vol119/issue3/images/large/JCS02826F1.jpeg
See also
- Signal transductionSignal transductionSignal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
- MorphogenesisMorphogenesisMorphogenesis , is the biological process that causes an organism to develop its shape...
- Developmental biologyDevelopmental biologyDevelopmental biology is the study of the process by which organisms grow and develop. Modern developmental biology studies the genetic control of cell growth, differentiation and "morphogenesis", which is the process that gives rise to tissues, organs and anatomy.- Related fields of study...
- EmbryogenesisEmbryogenesisEmbryogenesis is the process by which the embryo is formed and develops, until it develops into a fetus.Embryogenesis starts with the fertilization of the ovum by sperm. The fertilized ovum is referred to as a zygote...
- CancerCancerCancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
- CateninCateninCatenins are proteins found in complexes with cadherin cell adhesion molecules of animal cells. The first two catenins that were identified became known as alpha-catenin and beta-catenin. Alpha-catenin can bind to beta-catenin and can also bind actin. Beta-catenin binds the cytoplasmic domain of...