RTK class IV

As its name implies, fibroblast growth factor receptor is a receptor that binds to members of the fibroblast growth factor protein. Some of these receptors, and are involved in pathological conditions. For example, may lead to achondroplasia point mutations in FGFR3.

It consists of cell ligand domain, fibroblast growth factor receptor is composed of an intracellular domain having an immunoglobulin-like domains 3, the tyrosine kinase activity and transmembrane helix domain. These receptors, 22 members of the gene results (FGFR) fibroblast growth factor receptor family members up to fibroblast growth factor, ligand, 4 the production of different isoforms of 48 or more FGFR. I bind to growth factors including the The natural alternative splicing. Kinase domain and ligand-binding properties are different, however, immunoglobulin three areas such as (D1-D3) (Ig), therefore, is composed of the immunoglobulin superfamily, these isoforms are common I will be sharing the extracellular region of.

To the D1, D2, D3 – three immunoglobulin (Ig), such domains between D2 and D1, shows the growth of the acidic amino acids (“acid box”). This “box acid” can be involved in the regulation of FGF binding to FGFR. Immunoglobulin-like domain of D2 and D3, is sufficient for FGF binding. Each receptor can be activated by FGF of several factors. In most cases, I can factor FGF single also enable multiple receptors (for example, the FGFR Hani bind FGF1 seven basic). But FGF7, I can only FGFR2b and FGF18 is activated FGFR3 activation that has been shown recently. Further, the gene of the protein five FGFR, FGFR5, have been identified. When you as opposed to 1-4, lacks isoforms and cytoplasmic domain, the tyrosine kinase, the FGFR5γ, D2 and the extracellular domain of D1 only contains FGFR. It is known to dimerization, such as homodimers and hetero FGFR mother.

Fibroblast growth factor (of FGF), I make up a large family of polypeptide growth factors that are found in organisms ranging from humans to nematodes. Vertebrate molecular mass of the amino acid identity of 71% from 17-34 kDa Noto share 13, a member of the 22 in the range of FGF family. Among the vertebrates, stored and amino acid sequences gene structure is very FGF factor. High affinity, and FGF’s have a heparan sulfate required for the activation of either cell surface FGF receptors four for heparan sulfate proteoglycans. The embryonic development at the time, FGF’s is, have different roles in cell proliferation, in the regulation of differentiation and migration. In adult organisms, FGF’s is a function and homeostasis factor in response to injury and tissue repair. The phrase wrong, FGF Several factors may contribute to the pathogenesis of cancer. The family of expression FGF, it is important for signaling of nerve cells in the central and peripheral nervous system in adult tissue.

Exon 1 will include three exons encoding to include the start methionine original FGF gene, the coding portion of the FGF gene FGF several genes [1, 2]. (In FGF4 and FGF3) KB to 100 kilobytes or more that starts from the CUG codon upstream depends on the size less than 5, and has a 5 ‘transcribed sequence further. Start codon Some families, FGF these genes have been split between the (referred to as the 1A ~ 1D in the event of FGF8) sub splicing exons 4 FGF, exon 1 and 2, (exon 1a in The ATG) of the organization of this gene is maintained in zebrafish human, and mouse. It is used, but the effect of that feature is not understood. Subfamily of other FGF is, have the results from the use of alternative amino acid both ends alternative 5 ‘exon. Incidentally, it is unclear whether the 5 ‘untranslated exon splice general are used regulatory sequences and alternative promoter or exon thereof.

Adjustment (FGF) cell functions fibroblast growth factor was performed using the system in two receptors consisting of (HS) heparan sulfate receptor tyrosine kinases, and FGFR glycosaminoglycans. Mutations in N-glycosylation site specific potential human FGFR leads to phenotype for receptor overactivation specific. In order to ascertain whether it may affect the function of the FGFR membrane-bound receptors of the N-glycosylation of recombinant, soluble and was produced in Chinese hamster cells corresponding to the extracellular ligand-binding domain of FGFR1-IIIc. For the migration of 32 kDa corresponding to the molecular weight form which is expected of the deglycosylated receptor, heavily, is N-glycosylated, FGFR1-IIIc strip some between 75 kDa and 50 polypeptide to migrate on SDS-PAGE of the series has been observed. Quartz crystal microbalance dissipation binding assay the optical biosensor, indicating that the removal of N-glycans result of FGFR1-IIIc in increased binding of the receptor for the derived oligosaccharide substituted cell HS heparin and FGF 2 are. This effect is due to N-glycosylation of reducing the association rate constant of receptor for heparin oligosaccharides and FGF-2. N-glycans carrying two three sialic acid and / or one, and two, – was analyzed by mass spectrometry indicating the superiority of Koafukoshiru of complex type of glycan structure – and tri. The modeling glycan structures, such as receptor proteins, indicating that it may be disposed so as to interfere with the interaction of co-receptor or HS / at least a part of them and receptor ligands FGF strategically are. Thus, N-glycans receptor constitutes an additional pathway to modulate the activity of FGF factors.

The signaling by (FGFR3), to regulate matrix production of chondrocytes in the growth plate and in vitro and in vivo articular proliferation and differentiation are shown FGF receptor 3 fibroblast growth factor (FGF) 18 are. Specifically of FGFR3 lead or FGF18, the lack of congenital the addition of FGF18 in human articular chondrocytes in increased matrix production and expansion similar to the growth plate of fetal mouse, growth and culture. Based on other experiments and that these signals to promote cartilage production by chondrocytes through FGFR3 FGF18 has been suggested. Its role in cartilage formation has not been determined. Mice as a source of embryonic mesenchymal cells FGF18 signaling to determine how to affect cartilage formation – In this study, we used the FGFR3-/ and + / + limb bud FGFR3 . Confocal laser scanning microscopy showed damaged cartilage nodule formation in culture of FGFR3. Phenotype has been identified as impaired mitogenic response to FGF18, change of FGFR2 and expression FGFR1 expression of integrin receptors that have changed, as a result, causes the potential interaction of FGF18 stimulation disability and extracellular matrix In response to, and reduced the production of proteoglycan and type II collagen. The data FGF18, was identified as a selective ligand for FGFR3 in bud, limb mesenchymal cells to inhibit proliferation and promote the production of cartilage matrix and their differentiation. This work showing the FGFR3 and FGF18 intended for cartilage repair, the molecular potential targets for intervention in tissue engineering to restore the cartilage is damaged, thereby.