FGFR2

Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an essential role in the regulation of osteoblast differentiation, proliferation and apoptosis, and is required for normal skeleton development. Promotes cell proliferation in keratinocytes and imature osteoblasts, but promotes apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. FGFR2 signaling is down-regulated by ubiquitination, internalization and degradation. Mutations that lead to constitutive kinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signaling. Over-expressed FGFR2 promotes activation of STAT1.

FGFR2 Related Areas

Enzyme>>Protein Kinase>>Receptor Tyrosine Kinase>>FGFR2/CD332

Neuroscience>>Axon Guidance>>FGF & Receptor>>FGFR2/CD332

Signal Transduction>>Protein Kinase>>Receptor Tyrosine Kinase>>FGFR2/CD332

Stem Cell>>Neural Stem Cell (NSC)>>Glial Cell Markers>>FGFR2/CD332

Cancer>>Growth Factor & Receptor>>FGF & Receptor>>FGFR2/CD332

Cancer>>Growth Factor & Receptor>>Receptor Tyrosine Kinase>>FGFR2/CD332

Immunology>>Cluster of Differentiation>>Other>>FGFR2/CD332

FGFR2 Alternative Names

FGFR2, CD332, KGFR, ECT1, CFD1, CEK3, BEK, BFR-1, FLJ98662, JWS, K-SAM, TK14, TK25 [Homo sapiens]
Fgfr2, Fgfr-2, AU043015, AW556123, Bek, Fgfr-7, Fgfr7, KGFRTr, MGC102519, svs [Mus musculus]

Summaries for FGFR2

Entrez Gene summary for FGFR2:

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.

OMIM - description for FGFR2:

reported the crystal structure of the FGFR2 ectodomain in a dimeric form that is induced by simultaneous binding to FGF1 and a heparin decasaccharide. The complex is assembled around a central heparin molecule linking 2 FGF1 ligands into a dimer that bridges between 2 receptor chains. The asymmetric heparin binding involves contacts with both FGF1 molecules but only one receptor chain. The structure of the FGF1-FGFR2-heparin ternary complex provides a structural basis for the essential role of heparan sulfate in FGF signaling.

Wikipedia summary for FGFR2:

Fibroblast growth factor receptor 2 (FGFR2) also known as CD332 (cluster of differentiation 332) is a protein that in humans is encoded by the FGFR2 gene residing on chromosome 10.[1][2] FGFR2 is a receptor for fibroblast growth factor. 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.[3] 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 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.

Human FGFR2 Protein General Information

 

• Protein names: Fibroblast growth factor receptor 2 Short name=FGFR-2
• Sequence length: 821 AA.
• Domain: he second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans. Alternative splicing events affecting the third Ig-like domain are crucial for ligand selectivity.
• Sequence similarities: 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.
• Post-translational modification: Autophosphorylated. Binding of FGF family members together with heparan sulfate proteoglycan or heparin promotes receptor dimerization and autophosphorylation on several tyrosine residues. Autophosphorylation occurs in trans between the two FGFR molecules present in the dimer. Phosphorylation at Tyr-769 is essential for interaction with PLCG1.
• Subunit structure: Monomer. Homodimer after ligand binding. Interacts predominantly with FGF1 and FGF2, but can also interact with FGF3, FGF4, FGF6, FGF7, FGF8, FGF9, FGF10, FGF17, FGF18 and FGF22 (in vitro). Ligand specificity is determined by tissue-specific expression of isoforms, and differences in the third Ig-like domain are crucial for ligand specificity. Isoform 1 has high affinity for FGF1 and FGF2, but low affinity for FGF7. Isoform 3 has high affinity for FGF1 and FGF7, and has much higher affinity for FGF7 than isoform 1 (in vitro). Affinity for fibroblast growth factors (FGFs) is increased by heparan sulfate glycosaminoglycans that function as coreceptors. Likewise, KLB increases the affinity for FGF19 and FGF21. Interacts with PLCG1, GRB2 and PAK4.
• Subcellular location: Cell membrane; Single-pass type I membrane protein. Golgi apparatus. Cytoplasmic vesicle. Note: Detected on osteoblast plasma membrane lipid rafts. After ligand binding, the activated receptor is rapidly internalized and degraded.
• Involvement in disease: Defects in FGFR2 are the cause of Crouzon syndrome (CS) [MIM:123500]; also called craniofacial dysostosis type I (CFD1). CS is an autosomal dominant syndrome characterized by craniosynostosis (premature fusion of the skull sutures), hypertelorism, exophthalmos and external strabismus, parrot-beaked nose, short upper lip, hypoplastic maxilla, and a relative mandibular prognathism.

General information above from UniProt

Function for FGFR2 Protein

UniProtKB:

Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an essential role in the regulation of osteoblast differentiation, proliferation and apoptosis, and is required for normal skeleton development. Promotes cell proliferation in keratinocytes and imature osteoblasts, but promotes apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol-1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. FGFR2 signaling is down-regulated by ubiquitination, internalization and degradation. Mutations that lead to constitutive kinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signaling. Over-expressed FGFR2 promotes activation of STAT1.

Genatlas:

• receptor tyrosine kinase class IV, keratinocyte growth factor receptor, involved in vertebral development
• important regulator of bone formation and osteoblast activity, playing an important role in regulation of RUNX2 function and bone formation
• mediate two independent signaling pathways in retinal pigment epithelial cells
• FGFR2 playing distinct roles in proliferation and Sertoli cell differentiation during testis development
• FGFR2 signalling may be potentially a regulator of the NMD (nonsense-mediated decay) pathway
• maintains a critical balance between the proliferation and differentiation of osteoprogenitor cells

Homology for human FGFR2

• homolog to rattus Fgfr2 (97.19 pc)
• homolog to murine Fgfr2 (96.95 pc)

Phenotype Information for FGFR2

• Gene/Locus: FGFR2, BEK, CFD1, JWS
• Phenotype: Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis

Phenotype Information for FGFR2 from OMIM (Online Mendelian Inheritance in Man)

Drugs for FGFR2

Drugs for FGFR2 from TTD (Therapeutic Targets Database)