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FGFR2


Official Full Name
fibroblast growth factor receptor 2
Organism
Homo sapiens
Gene ID
2263
Background
The protein encoded by this gene is a member of the fibroblast growth factor receptor 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 is a high-affinity receptor for acidic, basic and/or keratinocyte growth factor, depending on the isoform. Mutations in this gene are associated with Crouzon syndrome, Pfeiffer syndrome, Craniosynostosis, Apert syndrome, Jackson-Weiss syndrome, Beare-Stevenson cutis gyrata syndrome, Saethre-Chotzen syndrome, and syndromic craniosynostosis. Multiple alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jan 2009]
Synonyms
BEK; JWS; BBDS; CEK3; CFD1; ECT1; KGFR; TK14; TK25; BFR-1; CD332; K-SAM
Bio Chemical Class
Kinase
Protein Sequence
MVSWGRFICLVVVTMATLSLARPSFSLVEDTTLEPEEPPTKYQISQPEVYVAAPGESLEVRCLLKDAAVISWTKDGVHLGPNNRTVLIGEYLQIKGATPRDSGLYACTASRTVDSETWYFMVNVTDAISSGDDEDDTDGAEDFVSENSNNKRAPYWTNTEKMEKRLHAVPAANTVKFRCPAGGNPMPTMRWLKNGKEFKQEHRIGGYKVRNQHWSLIMESVVPSDKGNYTCVVENEYGSINHTYHLDVVERSPHRPILQAGLPANASTVVGGDVEFVCKVYSDAQPHIQWIKHVEKNGSKYGPDGLPYLKVLKAAGVNTTDKEIEVLYIRNVTFEDAGEYTCLAGNSIGISFHSAWLTVLPAPGREKEITASPDYLEIAIYCIGVFLIACMVVTVILCRMKNTTKKPDFSSQPAVHKLTKRIPLRRQVTVSAESSSSMNSNTPLVRITTRLSSTADTPMLAGVSEYELPEDPKWEFPRDKLTLGKPLGEGCFGQVVMAEAVGIDKDKPKEAVTVAVKMLKDDATEKDLSDLVSEMEMMKMIGKHKNIINLLGACTQDGPLYVIVEYASKGNLREYLRARRPPGMEYSYDINRVPEEQMTFKDLVSCTYQLARGMEYLASQKCIHRDLAARNVLVTENNVMKIADFGLARDINNIDYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLMWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRILTLTTNEEYLDLSQPLEQYSPSYPDTRSSCSSGDDSVFSPDPMPYEPCLPQYPHINGSVKT
Open
Disease
Alzheimer disease, Bladder cancer, Breast cancer, Hepatitis virus infection, Liver cancer, Myeloproliferative neoplasm, Oral mucositis, Periodontal disease, Retina cancer, Solid tumour/cancer, Stomach cancer
Approved Drug
3 +
Clinical Trial Drug
9 +
Discontinued Drug
1 +

Cat.No. Product Name Price
AD06232Z Human FGFR2 adenoviral particles Inquiry
Cat.No. Product Name Price
SHH058729 shRNA set against Mouse Fgfr2(NM_201601.2) Inquiry
SHH294697 shRNA set against Rat FGFR2 (NM_001109892.1) Inquiry
SHH058673 shRNA set against Mouse Fgfr2(NM_010207.2) Inquiry
SHH294689 shRNA set against Human FGFR2 (NM_000141.4) Inquiry
SHH294693 shRNA set against Mouse FGFR2 (NM_010207.2) Inquiry
SHW005814 shRNA set against Chicken FGFR2 (NM_205319) Inquiry
SHW013915 shRNA set against Danio rerio FGFR2 (NM_001243004) Inquiry
SHW013916 shRNA set against Danio rerio FGFR2 (NM_001243005) Inquiry
SHW013917 shRNA set against Danio rerio FGFR2 (NM_001243006) Inquiry
SHW015485 shRNA set against Danio rerio FGFR2 (NM_178303) Inquiry
Cat.No. Product Name Price
CDCB167289 Chicken FGFR2 ORF Clone (NM_205319) Inquiry
CDFH006861 Human FGFR2 cDNA Clone(NM_001144918.1) Inquiry
CDFH006862 Human FGFR2 cDNA Clone(NM_001144917.1) Inquiry
CDFH006863 Human FGFR2 cDNA Clone(NM_001144919.1) Inquiry
CDFL004658 Mouse Fgfr2 cDNA Clone(NM_010207.2) Inquiry
CDFL004659 Mouse Fgfr2 cDNA Clone(NM_201601.2) Inquiry
CDFR009211 Rat Fgfr2 cDNA Clone(NM_001109892.1) Inquiry
CDFR009212 Rat Fgfr2 cDNA Clone(NM_001109893.1) Inquiry
CDFR009213 Rat Fgfr2 cDNA Clone(NM_001109894.1) Inquiry
CDFR009214 Rat Fgfr2 cDNA Clone(NM_001109895.1) Inquiry
CDFH006860 Human FGFR2 cDNA Clone(NM_001144916.1) Inquiry
CDFR009215 Rat Fgfr2 cDNA Clone(NM_001109896.1) Inquiry
MiUTR1M-04706 FGFR2 miRNA 3'UTR clone Inquiry
MiUTR3H-01920 FGFR2 miRNA 3'UTR clone Inquiry
MiUTR3H-01921 FGFR2 miRNA 3'UTR clone Inquiry
MiUTR3H-01922 FGFR2 miRNA 3'UTR clone Inquiry
MiUTR3H-01923 FGFR2 miRNA 3'UTR clone Inquiry
MiUTR3H-01924 FGFR2 miRNA 3'UTR clone Inquiry
MiUTR3H-01925 FGFR2 miRNA 3'UTR clone Inquiry
MiUTR3H-01926 FGFR2 miRNA 3'UTR clone Inquiry
MiUTR3H-01927 FGFR2 miRNA 3'UTR clone Inquiry
CDFR010525 Rat Fgfr2 cDNA Clone(NM_012712.1) Inquiry
CDFH006859 Human FGFR2 cDNA Clone(NM_001144915.1) Inquiry
CDFH006858 Human FGFR2 cDNA Clone(NM_001144913.1) Inquiry
CDFH006857 Human FGFR2 cDNA Clone(NM_001144914.1) Inquiry
CDCB175392 Danio rerio FGFR2 ORF Clone (NM_001243006) Inquiry
CDCB176960 Danio rerio FGFR2 ORF Clone (NM_178303) Inquiry
CDCL108191 Mouse Fgfr2 ORF clone (NM_010207.2) Inquiry
CDCL184269 Human FGFR2 ORF clone(NM_000141.4) Inquiry
MiUTR3H-01928 FGFR2 miRNA 3'UTR clone Inquiry
CDCR352239 Human FGFR2 ORF Clone(NM_001144917.1) Inquiry
SKO0083 FGFR2 Validated sgRNA vector Inquiry
CDCR376258 Rat Fgfr2 ORF Clone(NM_001109892.1) Inquiry
CDCR352238 Human FGFR2 ORF Clone(NM_001144916.1) Inquiry
CDCR352235 Human FGFR2 ORF Clone(NM_001144915.1) Inquiry
CDCR376259 Rat Fgfr2 ORF Clone(NM_001109893.1) Inquiry
CDCR277037 Mouse Fgfr2 ORF Clone(NM_201601.2) Inquiry
CDCR376260 Rat Fgfr2 ORF Clone(NM_001109894.1) Inquiry
CDCL108207 Human FGFR2 ORF clone (NM_001144913.1) Inquiry
CDCL108205 Human FGFR2 ORF clone (NM_001144919.1) Inquiry
CDCR376261 Rat Fgfr2 ORF Clone(NM_001109895.1) Inquiry
CDCB180715 Rabbit FGFR2 ORF clone (XM_008270457.1) Inquiry
CDCR376262 Rat Fgfr2 ORF Clone(NM_001109896.1) Inquiry
CDCR377572 Rat Fgfr2 ORF Clone(NM_012712.1) Inquiry
CDCB175391 Danio rerio FGFR2 ORF Clone (NM_001243005) Inquiry
CDCB175390 Danio rerio FGFR2 ORF Clone (NM_001243004) Inquiry
CDCR352241 Human FGFR2 ORF Clone(NM_001144918.1) Inquiry
CDCR352233 Human FGFR2 ORF Clone(NM_001144914.1) Inquiry

Detailed Information

FGFR2 gene, located on human chromosome 10q26, is a transmembrane protein with functions such as development regulating, and FGFR2 belongs to tyrosine kinase receptor. The structure of FGFR2 is mainly composed of three parts: extracellular region, transmembrane region and intracellular region. The extracellular region is a massive glycosylated ligand binding region consisting of three typical immunoglobulin (Ig) -like domains and acid regions between three domains, including Ig i, Ig ii, and Ig iii. Ig iii of FGFR2 is encoded by three exons, whose mRNA can be spliced alternately, making the C-terminal of Ig iii as a highly variable region. The diversity and specificity of ligand binding is determined by Ig iii of FGFR2. The transmembrane portion with a helical structure may be missing so as to form secretory FGFR2 and possess the ability to bind to FGFs. It is noted that FGFR2 transmembrane only happens once. The intracellular portion consists mainly of a domain with tyrosine kinase activity (TK1 and TK2). FGFR2, as a member of FGFRs, has three characteristics: (1) overlapping recognition and multi-specificity, that is, FGFR2 can bind to several FGFs with similar affinity; (2) FGFR2 binding to its ligand depends on cell surface heparin sulfate proteoglycan; (3) The same gene can produce many cytobinding and secretory FGFR2 receptors.

FGFR2 associated with Cholangiocarcinoma

Cholangiocarcinoma is an invasive tumor that originates from the bile duct. Unfortunately, most patients have advanced disease, so the survival rate is less than 2%. FGFR is abnormally activated in about 15% -20% of intrahepatic cholangiocarcinoma. FGFR has become an effective treatment strategy, which can benefit 70%-80% of patients with intrahepatic cholangiocarcinoma. Krook et al. have confirmed their hypothesis by using cell lines that can stably express these FGFR2 mutants to study the drug sensitivity in vitro. Through proteomic methods, they found that PI3K/Akt/ mTOR signaling pathway upregulated in cells expressing FGFR2p.e565a. In addition, they further tested the effect of mTOR inhibitors and confirmed that these cells were sensitive to FGFR2 inhibition. In conclusion, understanding how the secondary mutation of FGFR2 influences the sensitivity to different FGFR inhibitors and the development of reasonable combination therapy are very important to improve the clinical outcome of FGFR patients.

FGFR2 associated with breast cancer

FGFR2 is a member of the receptor tyrosine kinase subfamily, which also includes FGFR1, FGFR3, and FGFR4. There is increasing evidence that the FGF-FGFR2 signaling pathway plays an important role in breast cancer. Gene amplification and overexpression of FGFR2 in breast cancer tissues have also been described, especially in triple-negative breast cancer. Therefore, FGFR2 overexpression and inhibitor studies have been carried out using human cell models to support FGFR2's tumor-promoting function in breast cancer. The impact of crosstalk between FGFR2 and ER on the formation of tamoxifen resistance was studied by Sadej's group. They found that activation of the FGF7/FGFR2 axis could eliminate the growth inhibition of tamoxifen in cells exposed to medium with CAFs. It was also found that the activation of the PI3K/Akt pathway which targeted ER-Ser167 and the regulation of Bcl-2 expression after FGF7 treatment was the basis of FGFR2 to depend on tamoxifen resistance. Analysis of tissue samples with invasive ductal breast cancer revealed that the expression of FGFR2 was negatively correlated with the expression of ER. Their study has first demonstrated that the signaling pathways based on FGF7/ FGFR2 can regulate the function of the endoplasmic reticulum and influence the response between breast cancer cells and tamoxifen.

FGFR2Figure 1. FGFR2 paracrine signaling (Li et al., 2020).

References:

  1. Li F, Peiris M N, Donoghue D J. Functions of FGFR2 corrupted by translocations in intrahepatic cholangiocarcinoma[J]. Cytokine & growth factor reviews, 2020, 52: 56-67.
  2. Krook M A, Lenyo A, Wilberding M, et al. Efficacy of FGFR inhibitors and combination therapies for acquired resistance in FGFR2-fusion cholangiocarcinoma[J]. Molecular cancer therapeutics, 2020, 19(3): 847-857.
  3. Turczyk L, Kitowska K, Mieszkowska M, et al. FGFR2-driven signaling counteracts tamoxifen effect on ERα-positive breast cancer cells[J]. Neoplasia, 2017, 19(10): 791-804.
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