Description
It is a single-pass transmembrane protein composed of three extracellular Ig-like domains,a transmembrane region, and a tyrosine kinase domain (1, 2). Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic development (3, 4, 5, 6). Required for normal embryonicpatterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesisand skin development. Plays an essential role in the regulation of osteoblast differentiation, proliferation and apoptosis, and is required for normal skeleton development. Promotes cell proliferation in keratinocytes and immature osteoblasts, but promotes apoptosis indifferentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4 (7). Ligand binding leadsto the activation of several signalling cascades. Activation of PLCG1 leads to the productionof the cellular signalling molecules diacylglycerol and inositol 1,4,5-trisphosphate.Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, andmediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signallingpathway, as well as of the AKT1 signalling pathway (8). FGFR2 signalling is down-regulatedby ubiquitination, internalization and degradation. Mutations that lead to constitutivekinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signalling (9). Over-expressed FGFR2 promotes activation of STAT1.
FGFR2c is an alternatively spliced isoform representing mesenchymal variant of FGFR2