FGFR1 Recombinant Rabbit Monoclonal Antibody [SD08-25]

Function

Acidic and basic fibroblast growth factors (FGFs) are members of a family of multifunctional polypeptide growth factors that stimulate proliferation of cells of mesenchymal, epithelial and neuroectodermal origin. Like other growth factors, FGFs act by binding and activating specific cell surface receptors. These include the Flg receptor (FGFR-1), the Bek receptor (FGFR-2), FGFR-3, FGFR-4, FGFR-5 and FGFR-6. These receptors usually contain an extracellular ligand-binding region containing three immunoglobulin-like domains, a transmembrane domain and a cytoplasmic tyrosine kinase domain. The gene encoding human Flg maps to chromosome 8p12 and is alternatively spliced to produce several isoforms. Mutations in Flg are associated with Pfeiffer syndrome (a skeletal disorder characterized by craniosynostosis with deviation and enlargement of the thumbs and great toes), brachymesophalangy with phalangeal ankylosis and a varying degree of soft tissue syndactyly. The Flg gene is also involved in chromosomal translocations with ZNF198, CEP110 and FOP, which may lead to stem cell leukemia lymphoma (SCLL).

Background References

1. Lee C et al. VEGF-B prevents excessive angiogenesis by inhibiting FGF2/FGFR1 pathway. Signal Transduct Target Ther. 2023 Aug

2. Auffret L et al. A new subtype of diffuse midline glioma, H3 K27 and BRAF/FGFR1 co-altered: a clinico-radiological and histomolecular characterisation. Acta Neuropathol. 2023 Dec

Sequence Similarity

Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.

Tissue Specificity

Detected in astrocytoma, neuroblastoma and adrenal cortex cell lines. Some isoforms are detected in foreskin fibroblast cell lines, however isoform 17, isoform 18 and isoform 19 are not detected in these cells.

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 and proceeds in a highly ordered manner. Initial autophosphorylation at Tyr-653 increases the kinase activity by a factor of 50 to 100. After this, Tyr-583 becomes phosphorylated, followed by phosphorylation of Tyr-463, Tyr-766, Tyr-583 and Tyr-585. In a third stage, Tyr-654 is autophosphorylated, resulting in a further tenfold increase of kinase activity. Phosphotyrosine residues provide docking sites for interacting proteins and so are crucial for FGFR1 function and its regulation.; Ubiquitinated. FGFR1 is rapidly ubiquitinated by NEDD4 after autophosphorylation, leading to internalization and lysosomal degradation. CBL is recruited to activated FGFR1 via FRS2 and GRB2, and mediates ubiquitination and subsequent degradation of FGFR1.; N-glycosylated in the endoplasmic reticulum. The N-glycan chains undergo further maturation to an Endo H-resistant form in the Golgi apparatus.

Subcellular Location

Cell membrane, Nucleus, Cytoplasm, cytosol, Cytoplasmic vesicle.

UNIPROT

SwissProt: P11362 Human

Synonyms