FGFR-2 Antibody – Rat Monoclonal

Function: 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. Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and 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 in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. FGFR2 signaling is down-regulated by ubiquitination, internalization and degradation. Mutations that lead to constitutive kinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signaling. Over-expressed FGFR2 promotes activation of STAT1. Ref.6 Ref.7 Ref.11 Ref.13

Catalytic activity: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Enzyme regulation: Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by autophosphorylation on tyrosine residues

By similarity.

Subunit structure: Monomer. Homodimer after ligand binding. Interacts predominantly with FGF1 and FGF2, but can also interact with FGF3, FGF4, FGF6, FGF7, FGF8, FGF9, FGF10, FGF17, FGF18 and FGF22 (in vitro). Ligand specificity is determined by tissue-specific expression of isoforms, and differences in the third Ig-like domain are crucial for ligand specificity. Affinity for fibroblast growth factors (FGFs) is increased by heparan sulfate glycosaminoglycans that function as coreceptors. Likewise, KLB increases the affinity for FGF19 and FGF21. Interacts with PLCG1, GRB2 and PAK4

By similarity. Ref.7 Ref.13

Subcellular location: Cell membrane; Single-pass type I membrane protein. Golgi apparatus

By similarity. Cytoplasmic vesicle

By similarity. Note: Detected on osteoblast plasma membrane lipid rafts. After ligand binding, the activated receptor is rapidly internalized and degraded

By similarity.

Domain: The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans. Alternative splicing events affecting the third Ig-like domain are crucial for ligand selectivity

By similarity.

Post-translational modification: Autophosphorylated. Binding of FGF family members together with heparan sulfate proteoglycan or heparin promotes receptor dimerization and autophosphorylation on tyrosine residues. Autophosphorylation occurs in trans between the two FGFR molecules present in the dimer

By similarity. Ref.13N-glycosylated in the endoplasmic reticulum. The N-glycan chains undergo further maturation to an Endo H-resistant form in the Golgi apparatus

By similarity.Ubiquitinated. FGFR2 is rapidly ubiquitinated after autophosphorylation, leading to internalization and degradation. Subject to degradation both in lysosomes and by the proteasome

By similarity.

Disruption phenotype: Embryonic lethality shortly after implantation, due to trophoblast defects, absence of a functional placenta, failure of limb bud formation, plus defects in lung branching and heart development. Ref.8 Ref.9 Ref.10 Ref.12

Sequence similarities: Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.Contains 3 Ig-like C2-type (immunoglobulin-like) domains.Contains 1 protein kinase domain.