The Ror family of receptor tyrosine kinases consists of two structurally related proteins, Ror1 and Ror2. Ror1 is a pseudokinase that acts as a substrate for the oncogenic tyrosine kinase Met []. It is expressed during development []. It shows no significant expression in normal adult tissues, but it is selectively overexpressed in a number of malignancies []. Ror2 functions as a Wnt receptor required to maintain basal NMDAR-mediated synaptic transmission []. For a time its ligand remained elusive, hence the name receptor tyrosine kinase-like orphan receptor-2 (Ror2). It is now established that Wnt5A acts a ligand for Ror2 [].
The cysteine-rich domain (CRD) is an essential part of the tyrosine kinase-like orphan receptor (Ror) proteins, a conserved family of tyrosine kinases that function in various processes, including neuronal and skeletal development, cell polarity, and cell movement. Ror proteins are receptors of Wnt proteins, which are key players in a number of fundamental cellular processes in embryogenesis and postnatal development. In different cellular contexts, Ror proteins can either activate or repress transcription of Wnt target genes, and can modulate Wnt signaling by sequestering Wnt ligands. In addition, a number of Wnt-independent functions have been proposed for both Ror1 and Ror2 []. Proteins containing this domain also include CAM-1 from C. elegans. CAM-1 is a ROR receptor tyrosine kinase that inhibits the Wnt pathway [].
Frizzleds are seven transmembrane-spanning proteins that constitute an unconventional class of G protein-coupled receptors []. They have important regulatory roles during embryonic development [, ].Frizzleds expose their large N terminus on the extracellular side. The N-terminal, extracellular cysteine-rich domain (CRD) has been implicated as the Wnt binding domain and its structure has been solved []. The cysteine-rich domain of Frizzled (Fz) is shared with other receptor tyrosine kinases that have roles in development including the muscle-specific receptor tyrosine kinase (MuSK), the neuronal specific kinase (NSK2), and ROR1 and ROR2. The cytoplasmic side of many Fz proteins has been shown to interact with the PDZ domains of PSD-95 family members and is thought to have a role in the assembly of signalling complexes. The conserved cytoplasmic motif of Fz, Lys-Thr-X-X-X-Trp, is required for activation of the beta-catenin pathway, and for membrane localisation and phosphorylation of Dsh.In Drosophila melanogaster, the frizzled locus is involved in planar cell polarity, which is the coordination of the cytoskeleton of epidermal cells to produce a parallel array of cuticular hairs and bristles [, ]. In the wild-type wing, all hairs point towards the distal tip [], whereas in Fz mutants, the orientation of individual hairs with respect both to their neighbours and to the organism as a whole is altered. In the developing wing, Fz function is required for cells to respond to the extracellular polarity signal as well as the proximal-distal transmission of an intracellular polarity signal.In Caenorhabditis elegans, protein mom-5 is the equivalent of frizzled [].Three main signaling pathways are activated by agonist-activated Frizzled proteins: the Fz/beta-catenin pathway, the Fz/Ca2+ pathway and the Fz/PCP (planar cell polarity) pathway []. The Wnt/beta-catenin pathway is the best studied signalling pathway involving Fz receptors. In the Wnt/beta-catenin pathway the first downstream cytoplasmic components activated by Fz signalling include Dishevelled (Dsh) and/or its regulatory kinases.This entry represents frizzled-3 from vertebrates.
Frizzleds are seven transmembrane-spanning proteins that constitute an unconventional class of G protein-coupled receptors []. They have important regulatory roles during embryonic development [, ].Frizzleds expose their large N terminus on the extracellular side. The N-terminal, extracellular cysteine-rich domain (CRD) has been implicated as the Wnt binding domain and its structure has been solved []. The cysteine-rich domain of Frizzled (Fz) is shared with other receptor tyrosine kinases that have roles in development including the muscle-specific receptor tyrosine kinase (MuSK), the neuronal specific kinase (NSK2), and ROR1 and ROR2. The cytoplasmic side of many Fz proteins has been shown to interact with the PDZ domains of PSD-95 family members and is thought to have a role in the assembly of signalling complexes. The conserved cytoplasmic motif of Fz, Lys-Thr-X-X-X-Trp, is required for activation of the beta-catenin pathway, and for membrane localisation and phosphorylation of Dsh.In Drosophila melanogaster, the frizzled locus is involved in planar cell polarity, which is the coordination of the cytoskeleton of epidermal cells to produce a parallel array of cuticular hairs and bristles [, ]. In the wild-type wing, all hairs point towards the distal tip [], whereas in Fz mutants, the orientation of individual hairs with respect both to their neighbours and to the organism as a whole is altered. In the developing wing, Fz function is required for cells to respond to the extracellular polarity signal as well as the proximal-distal transmission of an intracellular polarity signal.In Caenorhabditis elegans, protein mom-5 is the equivalent of frizzled [].Three main signaling pathways are activated by agonist-activated Frizzled proteins: the Fz/beta-catenin pathway, the Fz/Ca2+ pathway and the Fz/PCP (planar cell polarity) pathway []. The Wnt/beta-catenin pathway is the best studied signalling pathway involving Fz receptors. In the Wnt/beta-catenin pathway the first downstream cytoplasmic components activated by Fz signalling include Dishevelled (Dsh) and/or its regulatory kinases.This entry represents frizzled-7. It is likely to have an important role in the maintenance of embryonic stem cells self-renewal capacity [].
Frizzleds are seven transmembrane-spanning proteins that constitute an unconventional class of G protein-coupled receptors []. They have important regulatory roles during embryonic development [, ].Frizzleds expose their large N terminus on the extracellular side. The N-terminal, extracellular cysteine-rich domain (CRD) has been implicated as the Wnt binding domain and its structure has been solved []. The cysteine-rich domain of Frizzled (Fz) is shared with other receptor tyrosine kinases that have roles in development including the muscle-specific receptor tyrosine kinase (MuSK), the neuronal specific kinase (NSK2), and ROR1 and ROR2. The cytoplasmic side of many Fz proteins has been shown to interact with the PDZ domains of PSD-95 family members and is thought to have a role in the assembly of signalling complexes. The conserved cytoplasmic motif of Fz, Lys-Thr-X-X-X-Trp, is required for activation of the beta-catenin pathway, and for membrane localisation and phosphorylation of Dsh.In Drosophila melanogaster, the frizzled locus is involved in planar cell polarity, which is the coordination of the cytoskeleton of epidermal cells to produce a parallel array of cuticular hairs and bristles [, ]. In the wild-type wing, all hairs point towards the distal tip [], whereas in Fz mutants, the orientation of individual hairs with respect both to their neighbours and to the organism as a whole is altered. In the developing wing, Fz function is required for cells to respond to the extracellular polarity signal as well as the proximal-distal transmission of an intracellular polarity signal.In Caenorhabditis elegans, protein mom-5 is the equivalent of frizzled [].Three main signaling pathways are activated by agonist-activated Frizzled proteins: the Fz/beta-catenin pathway, the Fz/Ca2+ pathway and the Fz/PCP (planar cell polarity) pathway []. The Wnt/beta-catenin pathway is the best studied signalling pathway involving Fz receptors. In the Wnt/beta-catenin pathway the first downstream cytoplasmic components activated by Fz signalling include Dishevelled (Dsh) and/or its regulatory kinases.This entry represents frizzled-4. Together with frizzled-8, it has a major role in controlling ureteric growth in the developing kidney [].
Frizzleds are seven transmembrane-spanning proteins that constitute an unconventional class of G protein-coupled receptors []. They have important regulatory roles during embryonic development [, ].Frizzleds expose their large N terminus on the extracellular side. The N-terminal, extracellular cysteine-rich domain (CRD) has been implicated as the Wnt binding domain and its structure has been solved []. The cysteine-rich domain of Frizzled (Fz) is shared with other receptor tyrosine kinases that have roles in development including the muscle-specific receptor tyrosine kinase (MuSK), the neuronal specific kinase (NSK2), and ROR1 and ROR2. The cytoplasmic side of many Fz proteins has been shown to interact with the PDZ domains of PSD-95 family members and is thought to have a role in the assembly of signalling complexes. The conserved cytoplasmic motif of Fz, Lys-Thr-X-X-X-Trp, is required for activation of the beta-catenin pathway, and for membrane localisation and phosphorylation of Dsh.In Drosophila melanogaster, the frizzled locus is involved in planar cell polarity, which is the coordination of the cytoskeleton of epidermal cells to produce a parallel array of cuticular hairs and bristles [, ]. In the wild-type wing, all hairs point towards the distal tip [], whereas in Fz mutants, the orientation of individual hairs with respect both to their neighbours and to the organism as a whole is altered. In the developing wing, Fz function is required for cells to respond to the extracellular polarity signal as well as the proximal-distal transmission of an intracellular polarity signal.In Caenorhabditis elegans, protein mom-5 is the equivalent of frizzled [].Three main signaling pathways are activated by agonist-activated Frizzled proteins: the Fz/beta-catenin pathway, the Fz/Ca2+ pathway and the Fz/PCP (planar cell polarity) pathway []. The Wnt/beta-catenin pathway is the best studied signalling pathway involving Fz receptors. In the Wnt/beta-catenin pathway the first downstream cytoplasmic components activated by Fz signalling include Dishevelled (Dsh) and/or its regulatory kinases.This entry represents frizzled-10 [], which may act as a receptor for Wnt-7a [].
Frizzleds are seven transmembrane-spanning proteins that constitute an unconventional class of G protein-coupled receptors []. They have important regulatory roles during embryonic development [, ].Frizzleds expose their large N terminus on the extracellular side. The N-terminal, extracellular cysteine-rich domain (CRD) has been implicated as the Wnt binding domain and its structure has been solved []. The cysteine-rich domain of Frizzled (Fz) is shared with other receptor tyrosine kinases that have roles in development including the muscle-specific receptor tyrosine kinase (MuSK), the neuronal specific kinase (NSK2), and ROR1 and ROR2. The cytoplasmic side of many Fz proteins has been shown to interact with the PDZ domains of PSD-95 family members and is thought to have a role in the assembly of signalling complexes. The conserved cytoplasmic motif of Fz, Lys-Thr-X-X-X-Trp, is required for activation of the beta-catenin pathway, and for membrane localisation and phosphorylation of Dsh.In Drosophila melanogaster, the frizzled locus is involved in planar cell polarity, which is the coordination of the cytoskeleton of epidermal cells to produce a parallel array of cuticular hairs and bristles [, ]. In the wild-type wing, all hairs point towards the distal tip [], whereas in Fz mutants, the orientation of individual hairs with respect both to their neighbours and to the organism as a whole is altered. In the developing wing, Fz function is required for cells to respond to the extracellular polarity signal as well as the proximal-distal transmission of an intracellular polarity signal.In Caenorhabditis elegans, protein mom-5 is the equivalent of frizzled [].Three main signaling pathways are activated by agonist-activated Frizzled proteins: the Fz/beta-catenin pathway, the Fz/Ca2+ pathway and the Fz/PCP (planar cell polarity) pathway []. The Wnt/beta-catenin pathway is the best studied signalling pathway involving Fz receptors. In the Wnt/beta-catenin pathway the first downstream cytoplasmic components activated by Fz signalling include Dishevelled (Dsh) and/or its regulatory kinases.This entry represents frizzled-1 and 2. Human frizzled-1 []is a functional partner for certain Wnts in inducing TCF dependent transcription []. Frizzled-2 has been reported to bind Wnt-8 [].
Frizzleds are seven transmembrane-spanning proteins that constitute an unconventional class of G protein-coupled receptors []. They have important regulatory roles during embryonic development [, ].Frizzleds expose their large N terminus on the extracellular side. The N-terminal, extracellular cysteine-rich domain (CRD) has been implicated as the Wnt binding domain and its structure has been solved []. The cysteine-rich domain of Frizzled (Fz) is shared with other receptor tyrosine kinases that have roles in development including the muscle-specific receptor tyrosine kinase (MuSK), the neuronal specific kinase (NSK2), and ROR1 and ROR2. The cytoplasmic side of many Fz proteins has been shown to interact with the PDZ domains of PSD-95 family members and is thought to have a role in the assembly of signalling complexes. The conserved cytoplasmic motif of Fz, Lys-Thr-X-X-X-Trp, is required for activation of the beta-catenin pathway, and for membrane localisation and phosphorylation of Dsh.In Drosophila melanogaster, the frizzled locus is involved in planar cell polarity, which is the coordination of the cytoskeleton of epidermal cells to produce a parallel array of cuticular hairs and bristles [, ]. In the wild-type wing, all hairs point towards the distal tip [], whereas in Fz mutants, the orientation of individual hairs with respect both to their neighbours and to the organism as a whole is altered. In the developing wing, Fz function is required for cells to respond to the extracellular polarity signal as well as the proximal-distal transmission of an intracellular polarity signal.In Caenorhabditis elegans, protein mom-5 is the equivalent of frizzled [].Three main signaling pathways are activated by agonist-activated Frizzled proteins: the Fz/beta-catenin pathway, the Fz/Ca2+ pathway and the Fz/PCP (planar cell polarity) pathway []. The Wnt/beta-catenin pathway is the best studied signalling pathway involving Fz receptors. In the Wnt/beta-catenin pathway the first downstream cytoplasmic components activated by Fz signalling include Dishevelled (Dsh) and/or its regulatory kinases.There are secreted forms of Fz, known as soluble or secreted frizzled-related proteins (sFRPS), which function as modulators of Wnt signaling through direct interaction with Wnts []. They consist of only the amino-terminal cysteine rich domain (CRD), but no transmembrane segments. These secreted forms may bind to Wnt proteins in solution and thereby change the activity of Wnts. Such as FRP/FrzB, which consist of the CRD only and can act as secreted antagonists of Wnt signalling.This entry includes both frizzled proteins and secreted frizzled-related proteins (SFRP).
Frizzleds are seven transmembrane-spanning proteins that constitute an unconventional class of G protein-coupled receptors []. They have important regulatory roles during embryonic development [, ].Frizzleds expose their large N terminus on the extracellular side. The N-terminal, extracellular cysteine-rich domain (CRD) has been implicated as the Wnt binding domain and its structure has been solved []. The cysteine-rich domain of Frizzled (Fz) is shared with other receptor tyrosine kinases that have roles in development including the muscle-specific receptor tyrosine kinase (MuSK), the neuronal specific kinase (NSK2), and ROR1 and ROR2. The cytoplasmic side of many Fz proteins has been shown to interact with the PDZ domains of PSD-95 family members and is thought to have a role in the assembly of signalling complexes. The conserved cytoplasmic motif of Fz, Lys-Thr-X-X-X-Trp, is required for activation of the beta-catenin pathway, and for membrane localisation and phosphorylation of Dsh.In Drosophila melanogaster, the frizzled locus is involved in planar cell polarity, which is the coordination of the cytoskeleton of epidermal cells to produce a parallel array of cuticular hairs and bristles [, ]. In the wild-type wing, all hairs point towards the distal tip [], whereas in Fz mutants, the orientation of individual hairs with respect both to their neighbours and to the organism as a whole is altered. In the developing wing, Fz function is required for cells to respond to the extracellular polarity signal as well as the proximal-distal transmission of an intracellular polarity signal.In Caenorhabditis elegans, protein mom-5 is the equivalent of frizzled [].Three main signaling pathways are activated by agonist-activated Frizzled proteins: the Fz/beta-catenin pathway, the Fz/Ca2+ pathway and the Fz/PCP (planar cell polarity) pathway []. The Wnt/beta-catenin pathway is the best studied signalling pathway involving Fz receptors. In the Wnt/beta-catenin pathway the first downstream cytoplasmic components activated by Fz signalling include Dishevelled (Dsh) and/or its regulatory kinases.This entry represents Frizzled-6. Frizzled-6 deficiency results in a severe midbrain morphogenesis defect in mice []. In humans, mutations in Frizzled-6 have been described to cause nail dysplasia [].
Frizzleds are seven transmembrane-spanning proteins that constitute an unconventional class of G protein-coupled receptors []. They have important regulatory roles during embryonic development [, ].Frizzleds expose their large N terminus on the extracellular side. The N-terminal, extracellular cysteine-rich domain (CRD) has been implicated as the Wnt binding domain and its structure has been solved []. The cysteine-rich domain of Frizzled (Fz) is shared with other receptor tyrosine kinases that have roles in development including the muscle-specific receptor tyrosine kinase (MuSK), the neuronal specific kinase (NSK2), and ROR1 and ROR2. The cytoplasmic side of many Fz proteins has been shown to interact with the PDZ domains of PSD-95 family members and is thought to have a role in the assembly of signalling complexes. The conserved cytoplasmic motif of Fz, Lys-Thr-X-X-X-Trp, is required for activation of the beta-catenin pathway, and for membrane localisation and phosphorylation of Dsh.In Drosophila melanogaster, the frizzled locus is involved in planar cell polarity, which is the coordination of the cytoskeleton of epidermal cells to produce a parallel array of cuticular hairs and bristles [, ]. In the wild-type wing, all hairs point towards thedistal tip [], whereas in Fz mutants, the orientation of individual hairs with respect both to their neighbours and to the organism as a whole is altered. In the developing wing, Fz function is required for cells to respond to the extracellular polarity signal as well as the proximal-distal transmission of an intracellular polarity signal.In Caenorhabditis elegans, protein mom-5 is the equivalent of frizzled [].Three main signaling pathways are activated by agonist-activated Frizzled proteins: the Fz/beta-catenin pathway, the Fz/Ca2+ pathway and the Fz/PCP (planar cell polarity) pathway []. The Wnt/beta-catenin pathway is the best studied signalling pathway involving Fz receptors. In the Wnt/beta-catenin pathway the first downstream cytoplasmic components activated by Fz signalling include Dishevelled (Dsh) and/or its regulatory kinases.This entry represents the cysteine-rich Wnt-binding domain (CRD) of Frizzled-5 (Fz5). The cysteine-rich domain (CRD) is an essential extracellular portion of the Fz5 receptor, and is required for binding Wnt proteins [].
