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The protein encoded by this gene is a member of the fibroblast growth factor receptor (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 factors, 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. Mutations in this gene have been associated with Pfeiffer syndrome, Jackson-Weiss syndrome, Antley-Bixler syndrome, osteoglophonic dysplasia, and autosomal dominant Kallmann syndrome 2. 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. [provided by RefSeq, Jul 2008]
FGFR1 is a member of the Fibroblast Growth Factor family, comprising of 4 receptors and 18 Ligands. FGFR1 signalling downstream functions mainly via PI3K and MAPK pathways (Turner et. al.). Several ways of involvement of FGFR1 in cancer have been proposed: auto- and paracrine activation, amplification and overexpression (Marshall et. al, Weiss et. al., Cheng et. al.). Especially amplification of FGFR1 in lung cancer is an emerging treatment target with clinical studies currently ongoing (e.g. NCT01004224). However, FGFR1 amplification does not always correlate with protein expression and predictive biomarkers still remain to be defined in clinic (von Mässenhausen et. al.). Mutation of FGFR1 seems to be less common, but has been described in glioblastoma, pilocytic astrocytomas and Ewing's sarcoma (Rand et. al., Jones et. al., Agelopoulos et. al.).
FGFR1 (Fibroblast Growth Factor Receptor 1) is a Protein Coding gene. Diseases associated with FGFR1 include Osteoglophonic Dysplasia and Hartsfield Syndrome. Among its related pathways are RET signaling and Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and transferase activity, transferring phosphorus-containing groups. An important paralog of this gene is FGFR2.
Fibroblast growth factors (FGFs) are mitogenic signaling molecules that have roles in angiogenesis, wound healing, cell migration, neural outgrowth and embryonic development. FGF receptors (FGFRs) are transmembrane catalytic receptors with intracellular tyrosine kinase activity.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0004672 | protein kinase activity | IEA | -- |
GO:0004713 | protein tyrosine kinase activity | IDA | 8622701 |
GO:0004714 | transmembrane receptor protein tyrosine kinase activity | IBA | 21873635 |
GO:0005007 | fibroblast growth factor-activated receptor activity | IBA,TAS | 2167437 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005576 | extracellular region | NAS | 1652059 |
GO:0005634 | nucleus | IEA | -- |
GO:0005737 | cytoplasm | IEA | -- |
GO:0005829 | cytosol | IEA | -- |
GO:0005886 | plasma membrane | TAS | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | RET signaling |
.92
|
.92
|
2 | Apoptotic Pathways in Synovial Fibroblasts |
Cellular Apoptosis Pathway
.85
Mitochondrial Apoptosis
.85
Apoptotic Pathways in Synovial Fibroblasts
.84
p53 Mediated Apoptosis
.84
DHA Signaling
.74
Telomerase Components in Cell Signaling
.72
PPAR Pathway
.66
|
Rac1 Pathway
.65
Actin-Based Motility by Rho Family GTPases
.62
ERK5 Signaling
.61
eIF2 Pathway
.60
Rap1 Pathway
.57
Nuclear Receptor Activation by Vitamin-A
.57
|
3 | GPCR Pathway |
Paxillin Interactions
.73
Ras Pathway
.73
GPCR Pathway
.62
Pancreatic Adenocarcinoma
.59
|
Breast Cancer Regulation by Stathmin1
.58
NFAT in Immune Response
.58
Estrogen Pathway
.55
P2Y Receptor Signaling
.38
|
4 | GAB1 signalosome |
.89
|
|
5 | Downstream signaling of activated FGFR2 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000122 | negative regulation of transcription by RNA polymerase II | IEA | -- |
GO:0000165 | MAPK cascade | TAS | -- |
GO:0001501 | skeletal system development | TAS | 7874169 |
GO:0001525 | angiogenesis | IEA | -- |
GO:0001657 | ureteric bud development | IEA | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Heparin | Approved, Investigational | Pharma | Antagonist, Target | 1058 | ||
Tyrosine | Approved, Investigational | Nutra | 1044 | |||
Lenvatinib | Approved, Investigational | Pharma | Target, inhibitor | Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors | 155 | |
Nintedanib | Approved | Pharma | Target, inhibitor | VEGFR, FGFR, PDGFR, and FLT3 inhibitor, Kinase Inhibitors | 145 | |
Palifermin | Approved | Pharma | Target, binder | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs |
---|
Compound | Action | Cas Number |
---|---|---|
ACTB-1003 | 939805-30-8 | |
AZD4547 | FGFR inhibitor | 1035270-39-3 |
BGJ398 | FGFR inhibitor ,potent and selective | 872511-34-7 |
CH5183284 (Debio-1347) | 1265229-25-1 | |
Dovitinib (TKI258) Lactate | Oral tyrosine kinase inhibitor (TKI) against FGFR1–3, VEGFR1–3, and platelet-derived growth factor receptor (PDGFR) | 915769-50-5 |
Dovitinib (TKI-258, CHIR-258) | Multitargeted RTK inhibitor | 405169-16-6 |
E-3810 | VEGF/FGF dual inhibitor, potent and selective | 1058137-23-7 |
KW 2449 | Multikinase inhibitor | 1000669-72-6 |
LY2874455 | FGF/FGFR Inhibitor | 1254473-64-7 |
NVP-BGJ398 phosphate | FGFR inhibitor | 1310746-10-1 |
Pazopanib Hydrochloride | VEGFR/PDGFR/FGFR/c-Kit/ c-Fms inhibitor | 635702-64-6 |
PD 161570 | 192705-80-9 | |
PD 173074 | FGFR inhibitor | 219580-11-7 |
SSR128129E | allosteric inhibitor of FGFR1, orally-active | 848318-25-2 |
SU 4312 | 5812-07-7 | |
TSU-68 (SU6668,Orantinib) | PDGFR/Flk-1/FGFR1 inhibitor,potent and competitive | 252916-29-3 |
Vandetanib (ZD6474) | VEGFR2/EGFR antagonist | 443913-73-3 |