FGFR1 Human, (22-374)
Description
Functional Role in Signaling Pathways
FGFR1 (22-374) mediates ligand-dependent activation of downstream pathways:
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FGF binding: Activates FGFR1 by inducing dimerization and trans-autophosphorylation of tyrosine residues (e.g., Y653/Y654 in the kinase domain) .
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Downstream signaling: Triggers MAPK/ERK, PI3K/AKT, and STAT pathways, regulating cell proliferation, survival, and differentiation .
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Pathological relevance: Overexpression or mutations in this region are linked to cancers (e.g., breast, lung) and developmental disorders (e.g., Pfeiffer syndrome) .
FGFR1 Amplification and Expression
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Squamous cell lung cancer (SQCLC):
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Colorectal cancer (CRC):
Therapeutic Targeting
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PD173074: An FGFR inhibitor reduces ERK1/2 activation and proliferation in FGFR1-amplified cancer cells .
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JNJ-42756493: A pan-FGFR inhibitor with IC<sub>50</sub> values of 1.2–5.7 nM against FGFR1–4, showing efficacy in FGFR-translocated cancers .
Experimental Applications of FGFR1 (22-374)
This recombinant fragment is widely used to study:
Product Specs
Fibroblast growth factor receptor 1 protein, also known as FGFR1, is encoded by the FGFR1 gene. This protein belongs to a family of four related proteins called fibroblast growth factor receptors. These receptors play crucial roles in various cellular pathways and processes, including cell growth regulation, maturation, division, embryonic development, and blood vessel formation.
Human FGFR1, produced in Sf9 insect cells, is a single, glycosylated polypeptide chain comprising 361 amino acids (22-374a.a.). It has a molecular mass of 40.1 kDa. However, on SDS-PAGE, the apparent molecular size will be approximately 40-57 kDa. This protein is expressed with an 8 amino acid His tag at the C-terminus and purified using proprietary chromatographic techniques.
The solution is colorless and sterile filtered.
The FGFR1 protein solution has a concentration of 0.5 mg/ml and is prepared in Phosphate Buffered Saline (pH 7.4) with 10% glycerol.
For short-term storage (2-4 weeks), the solution should be kept at 4°C. For longer periods, it's recommended to store it frozen at -20°C. To ensure long-term stability, consider adding a carrier protein (0.1% HSA or BSA). Repeated freezing and thawing should be avoided.
The purity is determined to be greater than 95.0% based on SDS-PAGE analysis.
Fibroblast growth factor receptor 1 isoform 2, FGFR 1a, bFGF-R-1, BFGFR, CD331, CEK, ECCL, FGFBR, FGFR-1, FLG, FLT-2, FLT2, HBGFR, HH2, HRTFDS, KAL2, N-SAM, OGD.
RPSPTLPEQA QPWGAPVEVE SFLVHPGDLL QLRCRLRDDV QSINWLRDGV QLAESNRTRI TGEEVEVQDS VPADSGLYAC VTSSPSGSDT TYFSVNVSDA LPSSEDDDDD DDSSSEEKET DNTKPNPVAP YWTSPEKMEK KLHAVPAAKT VKFKCPSSGT PNPTLRWLKN GKEFKPDHRI GGYKVRYATW SIIMDSVVPS DKGNYTCIVE NEYGSINHTY QLDVVERSPH RPILQAGLPA NKTVALGSNV EFMCKVYSDP QPHIQWLKHI EVNGSKIGPD NLPYVQILKT AGVNTTDKEM EVLHLRNVSF EDAGEYTCLA GNSIGLSHHS AWLTVLEALE ERPAVMTSPL YLELEHHHHH H
Q&A
What is FGFR1 Human (22-374) and how is it structurally characterized?
FGFR1 Human (22-374) represents the extracellular domain of the fibroblast growth factor receptor 1, spanning amino acids 22-374 of the full-length protein. This recombinant form is typically expressed as a single, glycosylated polypeptide chain with a molecular mass of 40.1kDa, though it may appear between 40-57kDa on SDS-PAGE due to glycosylation patterns . The protein belongs to the fibroblast growth factor receptor family, which includes four related proteins responsible for key cellular processes including growth regulation, maturation, cell division, embryonic development, and angiogenesis . When expressed in expression systems such as insect cells, it is often tagged (e.g., with His-tag) for purification purposes .
What are the alternative names and identifiers for FGFR1?
FGFR1 is known by multiple alternative names in scientific literature and databases:
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Fibroblast growth factor receptor 1 isoform 2
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FGFR 1a
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bFGF-R-1
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BFGFR
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CD331
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CEK
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ECCL
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FGFBR
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FGFR-1
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FLG
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FLT-2/FLT2
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HBGFR
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HH2
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HRTFDS
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KAL2
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N-SAM
This diversity of nomenclature reflects the protein's discovery in different contexts and its importance across multiple research fields.
What expression systems are optimal for producing functional FGFR1 Human (22-374)?
Insect cell expression systems, particularly Sf9 cells, are the preferred platform for producing recombinant FGFR1 Human (22-374) with proper folding and post-translational modifications . This system allows production of glycosylated protein that more closely resembles the native structure compared to bacterial expression systems. When expressing FGFR1 (22-374), researchers typically use baculovirus-based vectors with appropriate signal sequences and C-terminal purification tags (His or DDK/FLAG tags) . Expression in mammalian cells is also possible using vectors such as pCMV6-XL5-DDK-His or lentiviral systems like pLenti-C-Myc-DDK-P2A-Puro for stable expression studies .
What purification strategies yield the highest purity and activity for FGFR1 Human (22-374)?
Purification of FGFR1 Human (22-374) typically employs affinity chromatography utilizing the His-tag or other fusion tags incorporated into the recombinant construct. For highest purity (>95% as determined by SDS-PAGE), a multi-step purification approach is recommended :
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Initial capture using immobilized metal affinity chromatography (IMAC) for His-tagged protein
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Further purification using proprietary chromatographic techniques, which may include ion exchange chromatography to separate charge variants
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Size exclusion chromatography as a polishing step to remove aggregates and ensure monomeric protein
The purified protein is typically formulated in a stabilizing buffer containing phosphate-buffered saline (pH 7.4) with 10% glycerol for storage .
What are the key biological functions of FGFR1 in normal cellular processes?
FGFR1 plays crucial roles in multiple cellular processes and developmental pathways:
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Cell growth regulation through activation of downstream signaling cascades
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Cellular maturation and differentiation processes
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Cell division and proliferation control
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Embryonic development, particularly in pattern formation
These functions are mediated through the binding of fibroblast growth factors (FGFs) to the extracellular domain (22-374), triggering receptor dimerization and subsequent activation of intracellular signaling cascades including the MAPK and PI3K/AKT pathways. The extracellular domain is critical for ligand recognition and specificity .
How do structural alterations in the FGFR1 extracellular domain affect signaling outcomes?
Structural alterations in the FGFR1 extracellular domain (22-374) can significantly impact signaling outcomes. Particularly noteworthy are tail-to-tail rearrangements within the FGFR1 gene that result in various deletions in the extracellular region of the protein . These rearrangements can lead to:
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Loss of ectodomain components that enhance ligand-independent dimerization
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Constitutive activation of the receptor without ligand binding
How prevalent is FGFR1 amplification across different cancer types, and what are the implications?
FGFR1 amplification varies significantly across cancer types:
| Cancer Type | FGFR1 Amplification Rate | Citation |
|---|---|---|
| Squamous Cell Lung Carcinoma | 21% | |
| Lung Adenocarcinoma | 3% | |
| Bladder Cancer | Variable (subset of cases) |
What methodologies are optimal for detecting FGFR1 alterations in clinical samples?
Several complementary approaches are used to detect FGFR1 alterations in clinical samples:
The comprehensive assessment should include both genomic alterations (amplifications, mutations, rearrangements) and protein expression levels for optimal clinical decision-making.
How can researchers differentiate between FGFR1 gene amplification and functional protein overexpression?
Distinguishing between gene amplification and functional protein expression is critical for understanding FGFR1 biology and predicting therapeutic responses. A multi-faceted approach is recommended:
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Quantitative PCR and NGS: Determine copy number variation at the DNA level
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RNA-Seq or RT-qPCR: Measure mRNA expression levels to identify discrepancies between gene amplification and transcription
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Western Blotting: Quantify protein expression levels with phospho-specific antibodies to assess activation status
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Functional Assays: Employ cell-based assays to measure FGFR1-dependent signaling (e.g., ERK phosphorylation following FGF stimulation)
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Drug Sensitivity Testing: Determine IC50 values for FGFR inhibitors as a functional readout of FGFR1 dependency
Research has shown that cell lines with high FGFR1 amplification but low protein expression may exhibit resistance to FGFR inhibitors due to activation of alternative signaling pathways. Sensitivity to FGFR inhibitors correlates more strongly with protein and mRNA expression than with gene amplification alone .
What are the implications of tail-to-tail rearrangements within the FGFR1 gene for research and targeted therapy?
Tail-to-tail rearrangements within the FGFR1 gene represent an emerging area of research with significant implications:
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Structural Consequences: These rearrangements occur within the open reading frame but allow transcription of truncated FGFR1 protein using noncanonical in-frame ATG start codons, resulting in various deletions in the extracellular region
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Functional Impact: Loss of ectodomain components enhances ligand-independent dimerization, creating constitutively active FGFR1 variants
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Therapeutic Relevance: Approximately 50% of patients responding to FGFR inhibitors harbor these rearrangements, suggesting their potential value as biomarkers for therapy selection
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Detection Challenges: Standard gene amplification assays may miss these structural variations; targeted NGS approaches with appropriate bioinformatic pipelines are needed for detection
Research questions remain regarding how much FGFR1 mRNA and protein is expressed in tumors harboring these rearrangements, and whether specific structural changes correlate with particular functional outcomes or therapeutic vulnerabilities .
What are the optimal storage conditions for maintaining FGFR1 Human (22-374) activity?
For optimal stability and activity maintenance of FGFR1 Human (22-374), the following storage conditions are recommended:
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Short-term storage (2-4 weeks): Store at 4°C in the supplied buffer (typically phosphate-buffered saline, pH 7.4, with 10% glycerol)
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Long-term storage: Store at -20°C with the addition of a carrier protein (0.1% human serum albumin or bovine serum albumin) to prevent protein adsorption to vial surfaces
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Avoid freeze-thaw cycles: Multiple freeze-thaw cycles significantly reduce protein activity. Aliquot the protein before freezing to minimize the number of freeze-thaw cycles
When working with the protein, thaw aliquots rapidly and keep on ice to prevent degradation. The protein solution should appear as a sterile filtered colorless solution; any precipitation or turbidity indicates potential degradation .
Product Science Overview
Fibroblast Growth Factor Receptor-1 (FGFR1) is a crucial receptor tyrosine kinase involved in various cellular processes, including cell growth, differentiation, and angiogenesis. The recombinant form of FGFR1, specifically the amino acid sequence from 22 to 374, is often used in research to study its function and role in different biological pathways.
FGFR1 is composed of an extracellular region, a single transmembrane span, and an intracellular tyrosine kinase domain. The extracellular region includes three immunoglobulin-like domains (D1, D2, and D3), with D2 and D3 being essential for binding to fibroblast growth factors (FGFs) . The recombinant FGFR1 (22-374 a.a.) is expressed in insect cells and is a glycosylated polypeptide chain containing 361 amino acids .
FGFR1 plays a pivotal role in several biological processes:
- Cell Growth and Differentiation: FGFR1 signaling is crucial for the regulation of cell proliferation and differentiation. It is involved in the development of various tissues and organs during embryogenesis .
- Angiogenesis: FGFR1 is essential for the formation of new blood vessels, a process known as angiogenesis. This is particularly important in wound healing and tissue repair .
- Metabolism Regulation: FGFR1 signaling pathways are involved in the regulation of metabolic processes, including glucose and lipid metabolism .
The binding of FGFs to the extracellular domain of FGFR1 induces receptor dimerization and activation. This leads to the autophosphorylation of tyrosine residues in the intracellular domain, triggering downstream signaling pathways such as the MAPK, PI3K-AKT, and PLCγ pathways . These pathways ultimately result in various cellular responses, including proliferation, survival, and differentiation.
Aberrant FGFR1 signaling has been implicated in several diseases, including cancer. Overexpression or mutations in FGFR1 are associated with various cancers, such as lung, breast, and head and neck cancers . Targeting FGFR1 with specific inhibitors is being explored as a therapeutic strategy for these cancers.
The recombinant form of FGFR1 (22-374 a.a.) is used in research to study its structure, function, and interactions with other proteins. It is expressed in insect cells and purified to high purity levels . This recombinant protein is valuable for investigating the molecular mechanisms of FGFR1 signaling and for developing potential therapeutic interventions.
