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N-terminal GST-tagged, recombinant, human FGFR1 amino acids 456 - 765 containing the V561 mutation. The coordinates for recombinant human FGFR1 were described in Homann et al. (2001). Blencke et al. (2004) suggested mutations to a conserved threonine residue at the ATP binding site would result in inhibitor resistance. The amino acid valine 561 was mutated to a methionine in FGFR1 which corresponded to previously reported mutations found in Abl (T315) and EGFR (T766) which had been shown to confer resistance to selective inhibitors. Assay data for FGFR1 V561M had shown that this mutation had conferred resistance to PP58 (pyrido [2,3-d] pyrimidine tyrosine kinase inhibitor) compared to that of the wild type.
Alternate Names
Basic Fibroblast Growth Factor Receptor 1
c-fgr
CD331
References
Product Information
Presentation
Presented as a frozen solution in 50mM Tris/HCl pH 7.5, 300mM NaCl, 0.1mM EGTA, 0.03% Brij 35, 270mM sucrose, 1mM benzamidine, 0.2mM PMSF, 0.1% 2-mercaptoethanol.
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.
FUNCTION: SwissProt: P11362 # Receptor for basic fibroblast growth factor. A shorter form of the receptor could be a receptor for FGF1 (aFGF). SIZE: 822 amino acids; 91868 Da SUBUNIT: Interacts with SHB. Interacts with KLB (By similarity). SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. PTM: Binding of FGF1 and heparin promotes autophosphorylation on tyrosine residues and activation of the receptor. DISEASE: SwissProt: P11362 # Defects in FGFR1 are a cause of Pfeiffer syndrome (PS) [MIM:101600]; also known as acrocephalosyndactyly type V (ACS5). PS is characterized by craniosynostosis (premature fusion of the skull sutures) with deviation and enlargement of the thumbs and great toes, brachymesophalangy, with phalangeal ankylosis and a varying degree of soft tissue syndactyly. & Defects in FGFR1 are a cause of isolated hypogonadotropic hypogonadism (IHH) [MIM:146110]. Hypogonadism is a condition characterized by abnormally decreased gonadal function, with retardation of growth and sexual development. Hypogonadotropic hypogonadism is due to inadequate secretion of gonadotropins. It results from failure to release sufficient gonadotropin-releasing hormone. & Defects in FGFR1 are the cause of Kallmann syndrome type 2 (KAL2) [MIM:147950]; also known as hypogonadotropic hypogonadism and anosmia. 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 some cases, midline cranial anomalies (cleft lip/palate and imperfect fusion) are present and anosmia may be absent or inconspicuous. & Defects in FGFR1 are the cause of osteoglophonic dysplasia (OGD) [MIM:166250]; also known as osteoglophonic dwarfism. OGD is characterized by craniosynostosis, prominent supraorbital ridge, and depressed nasal bridge, as well as by rhizomelic dwarfism and nonossifying bone lesions. Inheritance is autosomal dominant. & Defects in FGFR1 are the cause of non-syndromic trigonocephaly [MIM:190440]; also known as metopic craniosynostosis. The term trigonocephaly describes the typical keel-shaped deformation of the forehead resulting from premature fusion of the frontal suture. Trigonocephaly may occur also as a part of a syndrome. & A chromosomal aberration involving FGFR1 may be a cause of stem cell leukemia lymphoma syndrome (SCLL). Translocation t(8;13)(p11;q12) with ZMYM2. SCLL usually presents as lymphoblastic lymphoma in association with a myeloproliferative disorder, often accompanied by pronounced peripheral eosinophilia and/or prominent eosinophilic infiltrates in the affected bone marrow. & A chromosomal aberration involving FGFR1 may be a cause of stem cell myeloproliferative disorder (MPD). Translocation t(6;8)(q27;p11) with FGFR1OP. Insertion ins(12;8)(p11;p11p22) with FGFR1OP2. MPD 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, FGFR1OP-FGFR1 or FGFR1-FGFR1OP may exhibit constitutive kinase activity and be responsible for the transforming activity. SIMILARITY: SwissProt: P11362 ## 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.
Molecular Weight
62.3kDa
Physicochemical Information
Dimensions
Materials Information
Toxicological Information
Safety Information according to GHS
Safety Information
Product Usage Statements
Quality Assurance
Routinely evaluated by phosphorylation of 500μM GGEEEEYFELVKKKK
Usage Statement
Unless otherwise stated in our catalog or other company documentation accompanying the product(s), our products are intended for research use only and are not to be used for any other purpose, which includes but is not limited to, unauthorized commercial uses, in vitro diagnostic uses, ex vivo or in vivo therapeutic uses or any type of consumption or application to humans or animals.
Storage and Shipping Information
Storage Conditions
Stable for 6 months at -70°C from date of shipment. Upon first use, rapidly thaw the vial under cold water and immediately place on ice. Aliquot unused material into pre-chilled microcentrifuge tubes and immediately snap-freeze the vials in liquid nitrogen prior to re-storage at -70°C.
Characterization of a conserved structural determinant controlling protein kinase sensitivity to selective inhibitors. Blencke S, Zech B, Engkvist O, Greff Z, Orfi L, Horvath Z, Keri G, Ullrich A, Daub H. Chemistry and Biology, 5:691-701 (2004)
2004
Expression and purification of human recombinant GST-FGF receptor-1. Homann S, Schacher B, Zumstein-Mecker S, Fabbro D, Bold G, Ferrari S. Journal of Biotechnology, 86:51-8 (2001)
2001
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