Fibroblast growth factor receptor 1
Encyclopedia
Fibroblast growth factor receptor 1 (FGFR1), also known as basic fibroblast growth factor receptor 1, fms-related tyrosine kinase-2 / Pfeiffer syndrome, and CD
331, is a receptor tyrosine kinase
whose ligands are specific members of the fibroblast growth factor
family. FGFR1 has been shown to be associated with Pfeiffer syndrome
.
(FGFR) family, where amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein consists of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factor
s, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. This particular family member binds both acidic and basic fibroblast growth factors and is involved in limb induction.
, Jackson-Weiss syndrome
, Antley-Bixler syndrome
, osteoglophonic dysplasia, squamous cell lung cancer (14) and autosomal dominant Kallmann syndrome
2. A few DNA sequence variants, including one nonsense mutation, have also been reported in isolated or non-syndromic cleft lip and palate. Clefts are a relatively common feature of Kallman syndrome as well. Somatic chromosomal aberrations involving this gene are associated with stem cell myeloproliferative disorder and stem cell leukemia lymphoma syndrome. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized.
with GRB14
, SHB
, FRS2
and FGF1
.
Cluster of differentiation
The cluster of differentiation is a protocol used for the identification and investigation of cell surface molecules present on white blood cells, providing targets for immunophenotyping of cells...
331, is a receptor tyrosine kinase
Receptor tyrosine kinase
Receptor tyrosine kinases s are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase proteins....
whose ligands are specific members of the fibroblast growth factor
Fibroblast growth factor
Fibroblast growth factors, or FGFs, are a family of growth factors involved in angiogenesis, wound healing, and embryonic development. The FGFs are heparin-binding proteins and interactions with cell-surface associated heparan sulfate proteoglycans have been shown to be essential for FGF signal...
family. FGFR1 has been shown to be associated with Pfeiffer syndrome
Pfeiffer syndrome
Pfeiffer syndrome is a rare genetic disorder characterized by the premature fusion of certain bones of the skull , which prevents further growth of the skull and affects the shape of the head and face...
.
Function
The protein encoded by this gene is a member of the fibroblast growth factor receptorFibroblast growth factor receptor
The fibroblast growth factor receptors are, as their name implies, receptors that bind to members of the fibroblast growth factor family of proteins. Some of these receptors are involved in pathological conditions...
(FGFR) family, where amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein consists of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factor
Fibroblast growth factor
Fibroblast growth factors, or FGFs, are a family of growth factors involved in angiogenesis, wound healing, and embryonic development. The FGFs are heparin-binding proteins and interactions with cell-surface associated heparan sulfate proteoglycans have been shown to be essential for FGF signal...
s, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. This particular family member binds both acidic and basic fibroblast growth factors and is involved in limb induction.
Clinical significance
Mutations in this gene have been associated with Pfeiffer syndromePfeiffer syndrome
Pfeiffer syndrome is a rare genetic disorder characterized by the premature fusion of certain bones of the skull , which prevents further growth of the skull and affects the shape of the head and face...
, Jackson-Weiss syndrome
Jackson-Weiss syndrome
Jackson-Weiss syndrome is a genetic disorder characterized by foot abnormalities and the premature fusion of certain bones of the skull , which prevents further growth of the skull and affects the shape of the head and face...
, Antley-Bixler syndrome
Antley-Bixler syndrome
Antley-Bixler syndrome, also called trapezoidocephaly-synostosis syndrome, is a rare, very severe autosomal recessive congenital disorder characterized by malformations and deformities affecting the majority of the skeleton and other areas of the body....
, osteoglophonic dysplasia, squamous cell lung cancer (14) and autosomal dominant Kallmann syndrome
Kallmann syndrome
Kallmann syndrome is a genetic disorder marked by anosmia and hypogonadism - the decreased functioning of the glands that produce sex hormones. Abnormalities in various genes may cause a defect in the hypothalamus, causing a deficiency of gonadotropin-releasing hormone ; this in turn causes...
2. A few DNA sequence variants, including one nonsense mutation, have also been reported in isolated or non-syndromic cleft lip and palate. Clefts are a relatively common feature of Kallman syndrome as well. Somatic chromosomal aberrations involving this gene are associated with stem cell myeloproliferative disorder and stem cell leukemia lymphoma syndrome. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized.
Interactions
Fibroblast growth factor receptor 1 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with GRB14
GRB14
Growth factor receptor-bound protein 14 is a protein that in humans is encoded by the GRB14 gene.-Interactions:GRB14 has been shown to interact with Epidermal growth factor receptor, Fibroblast growth factor receptor 1 and TNKS2.-Further reading:...
, SHB
SHB (gene)
SH2 domain-containing adapter protein B is a protein that in humans is encoded by the SHB gene.-Interactions:SHB has been shown to interact with Fibroblast growth factor receptor 1, Src, Linker of activated T cells, Lymphocyte cytosolic protein 2, ZAP-70, EPS8, PIK3R1 and VAV1.-Further reading:...
, FRS2
FRS2
Fibroblast growth factor receptor substrate 2 is a protein that in humans is encoded by the FRS2 gene.-Interactions:FRS2 has been shown to interact with PRKCI, Grb2, PTPN11, Fibroblast growth factor receptor 1, TrkA, Cbl gene and SOS1....
and FGF1
FGF1
Heparin-binding growth factor 1 is a protein that in humans is encoded by the FGF1 gene.-Interactions:FGF1 has been shown to interact with CSNK2B, CSNK2A2, HSPA9, S100A13, Casein kinase 2, alpha 1, Fibroblast growth factor receptor 1, FIBP, Fibroblast growth factor receptor 4, Fibroblast growth...
.
External links
- GeneReviews/NIH/NCBI/UW entry on FGFR-Related Craniosynostosis Syndromes
- GeneReviews/NCBI/NIH/UW entry on Kallmann syndrome
- Fibroblast growth factor receptor 1 on the Atlas of Genetics and OncologyAtlas of Genetics and Cytogenetics in Oncology and HaematologyThe Atlas of Genetics and Cytogenetics in Oncology and Haematology is a collection of resources on genes, chromosomes anomalies, leukemias, solid tumours, and cancer-prone diseases...