FGFR1
GeneName
FGFR1
Summary
FGFR1, also known as fibroblast growth factor receptor 1, FGFR-1, or MFR, is a 92 kDa transmembrane receptor that plays a vital role in various biological processes, including angiogenesis, cell migration, and differentiation. It is expressed in multiple tissues and is particularly important in developmental processes such as limb morphogenesis and inner ear development. FGFR1 is localised to the plasma membrane and can be found in the cytoplasm and nucleus, where it participates in signalling pathways initiated by fibroblast growth factors (FGFs). Its molecular functions include ATP binding, protein tyrosine kinase activity, and receptor-receptor interactions, which are crucial for mediating cellular responses to FGFs.
Importance
FGFR1 is relevant to: - Developmental biology, particularly in processes such as limb and ear morphogenesis, which are critical for proper organ formation - Cancer research, as aberrant FGFR1 signalling can lead to tumourigenesis and metastasis - Regenerative medicine, due to its role in cell proliferation and differentiation, making it a target for therapies aimed at tissue repair - Vascular biology, as it regulates angiogenesis and endothelial cell function, impacting conditions such as ischaemia and cardiovascular diseases
Top Products
For researchers investigating FGFR1, we recommend two excellent primary antibodies that cater to a variety of applications. The first is the well-cited polyclonal antibody, Anti-FGFR1 antibody (ab10646), which has garnered 78 citations and is particularly effective for immunohistochemistry (IHC) and immunocytochemistry (ICC). This antibody is a trusted choice for those looking to explore FGFR1 in tissue samples.In addition, we offer the recombinant antibody, Anti-FGFR1 antibody [EPR806Y] (ab76464), which has been validated in knockout models and is suitable for multiple applications, including Western blotting (WB), ICC, and immunoprecipitation (IP). With 44 citations, this recombinant product is ideal for researchers seeking the consistency and reliability that come with recombinant antibodies. Together, these antibodies provide a comprehensive toolkit for studying FGFR1 effectively.
Abcam Product Citation Summary
The data indicates that FGFR1 is being studied in various contexts, including cancer research, developmental biology, and tissue response to treatments. The use of different species, particularly human and mouse, highlights the relevance of FGFR1 in both basic and applied biomedical research.
Abcam Product Citation Table
Domain
The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans. Isoforms lacking the first Ig-like domain have higher affinity for fibroblast growth factors (FGF) and heparan sulfate proteoglycans than isoforms with all three Ig-like domains.
Function
Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration. Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Phosphorylates PLCG1, FRS2, GAB1 and SHB. 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. Promotes phosphorylation of SHC1, STAT1 and PTPN11/SHP2. In the nucleus, enhances RPS6KA1 and CREB1 activity and contributes to the regulation of transcription. FGFR1 signaling is down-regulated by IL17RD/SEF, and by FGFR1 ubiquitination, internalization and degradation.
Involvement in disease
Pfeiffer syndrome
PS
A syndrome characterized by the association of craniosynostosis, broad and deviated thumbs and big toes, and partial syndactyly of the fingers and toes. Three subtypes are known: mild autosomal dominant form (type 1); cloverleaf skull, elbow ankylosis, early death, sporadic (type 2); craniosynostosis, early demise, sporadic (type 3).
None
The disease is caused by variants affecting the gene represented in this entry.
Hypogonadotropic hypogonadism 2 with or without anosmia
HH2
A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).
None
The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. Some patients carrying mutations in FGFR1 also have a mutation other HH-associated genes including DUSP6, FGF8, FGF17, FLRT3, GNRH1, GNRHR, HS6ST1, IL17RD, ANOS1, KISS1R, NSMF, PROKR2, SPRY4 and TACR3 (PubMed:23643382).
Osteoglophonic dysplasia
OGD
Characterized by craniosynostosis, prominent supraorbital ridge, and depressed nasal bridge, as well as by rhizomelic dwarfism and nonossifying bone lesions. Inheritance is autosomal dominant.
None
The disease is caused by variants affecting the gene represented in this entry.
Hartsfield syndrome
HRTFDS
A syndrome characterized by the triad of holoprosencephaly, ectrodactyly, and cleft/lip palate. Profound intellectual disability is also present. Multiple other congenital anomalies usually occur.
None
The disease is caused by variants affecting the gene represented in this entry.
Trigonocephaly 1
TRIGNO1
A keel-shaped deformation of the forehead, caused by premature fusion of the metopic sutures. It results in a triangular shape of the head.
None
The disease is caused by variants affecting the gene represented in this entry.
Chromosomal aberrations involving FGFR1 are a cause of chromosome 8p11 myeloproliferative syndrome. Translocation t(8;13)(p11;q12) with ZMYM2. Translocation t(6;8)(q27;p11) with CEP43. Insertion ins(12;8)(p11;p11p22) with FGFR1OP2. Translocation t(8;9)(p12;q33) with CNTRL. Translocation t(2;8)(q12;p11) with RANBP2. Chromosome 8p11 myeloproliferative syndrome is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. The fusion proteins FGFR1OP2-FGFR1, CEP43-FGFR1 or FGFR1-CEP43 may exhibit constitutive kinase activity and be responsible for the transforming activity. The fusion protein CNTRL-FGFR1 is found in the cytoplasm, exhibits constitutive kinase activity and may be responsible for the transforming activity.
Encephalocraniocutaneous lipomatosis
ECCL
A sporadically occurring, neurocutaneous disorder characterized by ocular anomalies, skin lesions, and central nervous system anomalies. Clinical features include a well-demarcated hairless fatty nevus on the scalp, benign ocular tumors, intracranial and intraspinal lipomas, and congenital abnormalities of the meninges. Seizures, spasticity, and intellectual disability can be present.
None
The disease is caused by variants affecting the gene represented in this entry.
Jackson-Weiss syndrome
JWS
An autosomal dominant craniosynostosis syndrome characterized by craniofacial abnormalities and abnormality of the feet: broad great toes with medial deviation and tarsal-metatarsal coalescence.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
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.
Sequence Similarities
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.
Cellular localization
- Cell membrane
- Single-pass type I membrane protein
- Nucleus
- Cytoplasm
- Cytosol
- Cytoplasmic vesicle
- After ligand binding, both receptor and ligand are rapidly internalized. Can translocate to the nucleus after internalization, or by translocation from the endoplasmic reticulum or Golgi apparatus to the cytosol, and from there to the nucleus.
Alternative names
CD331, BFGFR, CEK, FGFBR, FLG, FLT2, HBGFR, FGFR1, Fibroblast growth factor receptor 1, FGFR-1, Basic fibroblast growth factor receptor 1, Fms-like tyrosine kinase 2, N-sam, Proto-oncogene c-Fgr, bFGF-R-1, FLT-2
Database links
swissprot:P11362 omim:136350 swissprot:O95684 entrezGene:2260
Other research areas
- Neuroscience