FGF Receptors Sample Clauses

FGF Receptors. Most FGF signalling is mediated by activation of FGF receptors (FGFR) proteins (Xxxx 2007). FGFRs belong to the family of receptor tyrosine kinases (RTKs).The FGFs exert their function through interactions between heparin-like proteoglycans and receptors (Xxxx 2007). They require the glycosaminoglycan (GAG) side chains of heparan sulphate proteoglycans (HSPG) for high affinity binding to their specific receptors (Xxxxx et al. 2009). Four high-affinity receptors have been identified for the FGF family, in humans and mice, named FGFR1 to FGFR4. These receptors are type I transmembrane proteins with an extracellular ligand-binding domain with three immunoglobulin domains (I, II, and III), a transmembrane domain, and a split intracellular tyrosine kinase domain (Itoh 2007). FGF proteins bind to FGFR proteins and induce their dimerization and the phosphorylation of specific cytoplasmic tyrosine residues (Itoh 2007). The phosphorylation of FGFRs triggers activation of cytoplasmic signal transduction pathways. This activation results in the activation of several signal transduction pathways eliciting different cell responses (Xxxx 2007). Phylogenetic analysis indicates potential evolutionary relationships in the gene family. Co-evolution has permitted the evolution of increased ligand-receptor specificity, enabling the formation of preferred ligand-receptor interactions (Xxxx 2007). In addition, the alternative splicing of FGFRs has increased their functional diversity. Several alternative splicing events take place following transcription of FGFR1, FGFR2 and FGFR3 and give rise to different isoforms with distinct functional properties (Xxxxx et al. 2009). Of particular importance to FGF binding specificity is the third Ig loop, the N-terminal half of which is encoded by an invariant IIIa exon with alternative usage of IIIb or IIIc exons for the C-terminal half (Xxxxxxxxx, Xxxxx, & Xxxxxxxx 2005). The immunoglobulin-like domain III is an essential determinant of ligand-binding specificity (Itoh 2007). As a general rule, FGFRs encoding exon IIIb (FGFR IIIb) are expressed on epithelial cells, whereas the FGFRs encoding exon IIIc (FGFR IIIc) are expressed on mesenchymal cells (Xxxxxxxxx, Xxxxx, & Xxxxxxxx 2005). By contrast, the ligands for FGFR IIIb are often expressed in mesenchymal cells, whereas ligands for FGFR IIIc are expressed in epithelial cells (Xxxxx et al. 2009;Xxxx 2007). This establishes a paracrine mechanism of signalling between epithelia and mesench...
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