FGFR2 antibody

Fibroblast growth factors (FGFs) are members of a large family of structurally related heparin binding polypeptides (17-38kD) that are potent physiological regulators of growth and differentiation for a wide variety of cells of mesodermal, ectodermal and endodermal origin. FGFs are substantially involved in normal development, wound healing and repair, angiogenesis, a variety of neurotrophic activities, in hematopoiesis as well as in tissue remodeling and maintenance. They have also been implicated in pathological conditions such as tumorigenesis and metastasis. The FGF family consists of at least seventeen members designated FGF1 through FGF17. To date, four genes encoding for high affinity cell surface FGF receptors (FGFRs) have been identified: FGFR1 [flg, cek-1], FGFR2 [bek, cek-3], FGFR3 [cek-2] and FGFR4. Multiple additional variants (isoforms) arising by alternative splicing have been reported. Soluble, secreted8 or possibly cleaved9 forms of FGFR1 and FGFR2 have also been found in body fluids or were artificially constructed. FGFRs are members of the tyrosine kinase family of growth factor receptors. They are glycosylated 110-150 kD proteins that are constructed of an extracellular ligand binding region with either two or typically three immunoglobulin (Ig)-like domains and an eight amino acid eacidic boxi, a transmembrane region and a cytoplasmic split tyrosine kinase domain that is activated following ligand binding and receptor dimerization. The ligand binding site of all FGFRs is confined to the extracellular Ig-like domains 2 and 3. FGFRs exhibit overlapping recognition and redundant specificity. One receptor type may bind several of the FGFs with a similar affinity. Also one FGF type may bind similarly to several distinct receptors. This accounts for the rather identical effects of different FGF ligands on common cell types. FGFs binding to cellular FGFRs depends on, or is markedly facilitated by the low-affinity interaction of FGFs with the polysaccharide component of cell surface or extracellular matrix heparan sulfate proteoglycans (HSPG). For example, perlecan, a basement membrane HSPG, promotes high affinity binding of FGF2 in vitro and angiogenesis in vivo. Signal transduction by FGFRs requires dimerization or oligomerization and autophosphorylation of the receptors through their tyrosine kinase domain. Subsequent association with cytoplasmic signaling molecules leads to DNA synthesis or differentiation. The signaling and biological responses elicited by distinct FGFRs substantially differ and are dictated by the intracellular domain. At the mRNA level, FGFR- 2 is highly expressed in developing human tissues including the brain (preferentially in glial cells), choroid plexus, skin, lung, kidney and bone. It is widely expressed in many adult human and animal tissues. It may be found in several anchorage-dependent cells, such as normal and malignant breast cancer cells. Crouzon as well as other craniosynostosis syndromes (e.g. Pfeifferis, Apertis, Jackson-Weissi), disorders of human skeletal development, have been shown to be the result of mutations in the extracellular domain of FGFR2.