Further (FGFR2), is a protein encoded by a gene present in FGFR2 10 on human chromosome fibroblast growth factor receptor 2 (called cluster differentiation 332) CD332. FGFR2 is a receptor for fibroblast growth factor. Amino acids are evolutionarily conserved and highly inter-member, wherein the protein the gene encodes is a member of the fibroblast growth factor receptor family. FGFR family members, are different from each other and tissue distribution affinity ligands thereof. The full-length protein typical immunoglobulin domains three transmembrane segments hydrophobic and consists of an extracellular region consisting of the cytoplasmic tyrosine kinase domain. Trigger a cascade of downstream signals affect the differentiation and mitosis Finally, the extracellular portion of the protein is reacted with fibroblast growth factor. Depending on the isoform family of this particular are high affinity receptors acidic, for keratinocyte growth factor and / or basic.
FGFR2, has FGFR2IIIc and isoforms FGFR2IIIb naturally occurring two that were created by splicing of immunoglobulin-like domain of the third. FGFR2IIIb is, internal organs and skin are found endothelial lining body and ectoderm derived tissue, in other words mainly. And craniofacial bone that are associated with craniosynostosis, therefore, including isoforms and mutations in this gene, FGFR2IIIc has become to mesenchyme.
FGFR2, the vessel and the bone in particular, it has an important role in tissue repair and embryogenesis. Like other members of the fibroblast growth factor receptor family, the receptor through that leads to the tyrosine kinase domain that initiates a cascade of intracellular signaling, coupled to (receptor binding) dimer and its ligand I want to output the signal. At the molecular level, these signals mediate the differentiation cell division and proliferation.
As mentioned, according to the mutation itself and suturing the skull FGFR2 mutation associated with craniosynostosis syndrome is a cranial defect caused by early fusion of other features of the disease. Analysis of chromosomal abnormalities in patients led to the identification and validation of FGFR2 locus as palate and / or cleft lip. At the molecular level, I affect the FGFR2IIIc associated with significant changes in proliferation and differentiation of osteoblasts mutation. I have considered changes in the FGFR2 signaling is the basis for the fusion syndrome. To date, there are two mechanisms of FGFR2 signal that has changed. Always, regardless of when it is associated with constitutive activation of the FGFR, FGFR2 receptor signaling amount of FGF ligand first. This mechanism is seen in patients with Pfeiffer syndrome and Crouzon. As a result of the FGF receptor binding factors that are not normally connected, a second associated with Apert syndrome is loss of specificity of FGFR2 isoforms.
Protein tyrosine kinases act as a receptor on the surface of cells in fibroblast growth factor plays an important role in the regulation of embryonic development and regulation of apoptotic cell proliferation, differentiation, and migration. You need a normal embryo modeling nutrient function, development of limb bud, morphogenesis of lung, bone formation, the development of skin. Plays an important role in the regulation of apoptosis osteoblast differentiation, and proliferation, and is required for normal development of the skeleton. It encourages cell growth in immature osteoblasts and keratinocytes, but promotes the apoptosis of osteoblasts differentiated. PAK4 and PLCG1, FRS2 phosphorus. Activating ligand results in signal transduction cascades few. Enabling triphosphate – inositol 1,4,5 and diacylglycerol of signaling molecules PLCG1 cell yield.
Phosphorylation of FRS2 is leading the recruitment of signaling pathways of Akt1-mediated activation of the RAS and SOS1 and GRB2, GAB1, PIK3R1, and MAP kinase signaling pathways MAPK1/ERK2, and MAPK3/ERK1. FGFR2 signaling It is down-regulated by the decomposition ubiquitination, and internalization. Or lead to constitutive activation kinase, mutations that affect the decomposition result mature FGFR2, and internalization of normal in abnormal signaling. FGFR2 overexpression promote the activation of STAT1
Fibroblast growth factor (a FGF) (FGF1 – 16-23 and 10) is a mitogenic signal transduction molecules that play a role in wound healing embryonic angiogenesis, cell migration, and neurite outgrowth. The FGF binds heparin sulfate glycosaminoglycan (HSGAGs) easily dimerization (activation) FGF receptor a (FGFR is). FGFR is a catalyst transmembrane receptor intracellular tyrosine kinases. genes of four people encoding the FGFR to produce, (FGFR1b, FGFR1c, FGFR2b, FGFR2c, FGFR3b, FGFR4 and FGFR3c) the different receptors of seven due to alternative splicing events both outside and occurred in the area of intracellular there. In alternative splicing isoforms, is a tissue-specific in general: B isoforms isoform is expressed in mesenchymal tissue, expressed in epithelial tissue. Cytoplasmic kinase domain can be activated and transphosphorylate the tyrosine residue, HSGAG-FGF-FGFR binding, to start the dimerization of FGFR. Further HSGAGs, stabilize the FGF-FGFR binding and functions to prevent deterioration of the FGF. There is evidence of crosstalk couple, and the Notch signaling pathway of FGFR MAPK intracellular signaling cascade PLCgamma, and PI3-K/Akt. Further, part of the active FGF-FGFR complexes is a function endocytosis and the cell nucleus and / or directly to the cytoplasm. Mutations in the FGFR genes, are the cause of developmental disorders of some human, which is characterized by skeletal abnormalities as may lead to cancer expression and cell transformation of strengthening FGFR with achondroplasia like this .