Fibroblast growth factor receptor 2
Also known as: BEK, FGFR2, KGFR, KSAM
Function
Tyrosine-protein kinase that acts as a 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 immature 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.
Classification
- Family (Pfam)
- PF07679 I-set, PF13927 Ig_3, PF07714 PK_Tyr_Ser-Thr
- InterPro
- FGF_rcpt_fam, Ig-like_dom, Ig-like_dom_sf, Ig-like_fold, Ig_I-set, Ig_sub, Ig_sub2, Kinase-like_dom_sf, Prot_kinase_dom, Protein_kinase_ATP_BS, RTK, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_AS, Tyr_kinase_cat_dom
- Functional cluster
- Protein Serine/Threonine Kinases
Experimental structures · PDB · 57
- 1DJS X-ray 2.40A
- 1E0O X-ray 2.80A
- 1EV2 X-ray 2.20A
- 1GJO X-ray 2.40A
- 1II4 X-ray 2.70A
- 1IIL X-ray 2.30A
- 1NUN X-ray 2.90A
- 1OEC X-ray 2.40A
- 1WVZ NMR
- 2FDB X-ray 2.28A
- 2PSQ X-ray 2.40A
- 2PVF X-ray 1.80A
- … and 45 more
A predicted model is available from AlphaFold.
Gene Ontology · 113
- GO:0005938 cell cortex
- GO:0009986 cell surface
- GO:0005737 cytoplasm
- GO:0031410 cytoplasmic vesicle
- GO:0060076 excitatory synapse
- GO:0005576 extracellular region
- GO:0005794 Golgi apparatus
- GO:0016020 membrane
- GO:0005634 nucleus
- GO:0005886 plasma membrane
- GO:0043235 receptor complex
- GO:0005524 ATP binding
- GO:0017134 fibroblast growth factor binding
- GO:0005007 fibroblast growth factor receptor activity
- GO:0008201 heparin binding
- GO:0042802 identical protein binding
- GO:0042803 protein homodimerization activity
- GO:0004713 protein tyrosine kinase activity
- GO:0001525 angiogenesis
- GO:0009887 animal organ morphogenesis
- GO:0006915 apoptotic process
- GO:0007409 axonogenesis
- GO:0060348 bone development
- GO:0030282 bone mineralization
- GO:0060349 bone morphogenesis
- GO:0060667 branch elongation involved in salivary gland morphogenesis
- GO:0060670 branching involved in labyrinthine layer morphogenesis
- GO:0060442 branching involved in prostate gland morphogenesis
- GO:0060445 branching involved in salivary gland morphogenesis
- GO:0048755 branching morphogenesis of a nerve
- GO:0060449 bud elongation involved in lung branching
- GO:0045165 cell fate commitment
- GO:0007267 cell-cell signaling
- GO:0071456 cellular response to hypoxia
- GO:0071300 cellular response to retinoic acid
- GO:0071560 cellular response to transforming growth factor beta stimulus
- GO:0048565 digestive tract development
- GO:0048701 embryonic cranial skeleton morphogenesis
- GO:0048557 embryonic digestive tract morphogenesis
- GO:0048568 embryonic organ development
- GO:0048562 embryonic organ morphogenesis
- GO:0009880 embryonic pattern specification
- GO:0003416 endochondral bone growth
- GO:0048730 epidermis morphogenesis
- GO:0030855 epithelial cell differentiation
- GO:0060664 epithelial cell proliferation involved in salivary gland morphogenesis
- GO:0001837 epithelial to mesenchymal transition
- GO:0008543 fibroblast growth factor receptor signaling pathway
- GO:0035603 fibroblast growth factor receptor signaling pathway involved in hemopoiesis
- GO:0035602 fibroblast growth factor receptor signaling pathway involved in negative regulation of apoptotic process in bone marrow cell
- GO:0035607 fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development
- GO:0035604 fibroblast growth factor receptor signaling pathway involved in positive regulation of cell proliferation in bone marrow
- GO:0022612 gland morphogenesis
- GO:0031069 hair follicle morphogenesis
- GO:0001701 in utero embryonic development
- GO:0042472 inner ear morphogenesis
- GO:0032808 lacrimal gland development
- GO:0060601 lateral sprouting from an epithelium
- GO:0060174 limb bud formation
- GO:0048286 lung alveolus development
- GO:0030324 lung development
- GO:0060463 lung lobe morphogenesis
- GO:0060484 lung-associated mesenchyme development
- GO:0060615 mammary gland bud formation
- GO:0003149 membranous septum morphogenesis
- GO:0048762 mesenchymal cell differentiation
- GO:0060915 mesenchymal cell differentiation involved in lung development
- GO:0060916 mesenchymal cell proliferation involved in lung development
- GO:0048333 mesodermal cell differentiation
- GO:0030901 midbrain development
- GO:0016331 morphogenesis of embryonic epithelium
- GO:0010839 negative regulation of keratinocyte proliferation
- GO:0000122 negative regulation of transcription by RNA polymerase II
- GO:0042476 odontogenesis
- GO:0021769 orbitofrontal cortex development
- GO:0035265 organ growth
- GO:0030916 otic vesicle formation
- GO:0003148 outflow tract septum morphogenesis
- GO:0018108 peptidyl-tyrosine phosphorylation
- GO:0090263 positive regulation of canonical Wnt signaling pathway
- GO:0060045 positive regulation of cardiac muscle cell proliferation
- GO:0045787 positive regulation of cell cycle
- GO:0051781 positive regulation of cell division
- GO:0008284 positive regulation of cell population proliferation
- GO:0050679 positive regulation of epithelial cell proliferation
- GO:0060501 positive regulation of epithelial cell proliferation involved in lung morphogenesis
- GO:0070374 positive regulation of ERK1 and ERK2 cascade
- GO:0043410 positive regulation of MAPK cascade
- GO:0002053 positive regulation of mesenchymal cell proliferation
- GO:0010518 positive regulation of phospholipase activity
- GO:0045944 positive regulation of transcription by RNA polymerase II
- GO:1904707 positive regulation of vascular associated smooth muscle cell proliferation
- GO:0030177 positive regulation of Wnt signaling pathway
- GO:0009791 post-embryonic development
- GO:0060527 prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis
- GO:0060523 prostate epithelial cord elongation
- GO:0060512 prostate gland morphogenesis
- GO:0046777 protein autophosphorylation
- GO:0021860 pyramidal neuron development
- GO:0070372 regulation of ERK1 and ERK2 cascade
- GO:0060688 regulation of morphogenesis of a branching structure
- GO:0045667 regulation of osteoblast differentiation
- GO:0033688 regulation of osteoblast proliferation
- GO:0051150 regulation of smooth muscle cell differentiation
- GO:0008589 regulation of smoothened signaling pathway
- GO:0048608 reproductive structure development
- GO:0045471 response to ethanol
- GO:0032496 response to lipopolysaccharide
- GO:0048705 skeletal system morphogenesis
- GO:0060529 squamous basal epithelial stem cell differentiation involved in prostate gland acinus development
- GO:0001657 ureteric bud development
- GO:0055010 ventricular cardiac muscle tissue morphogenesis
- GO:0021847 ventricular zone neuroblast division
Disease associations
- Apert syndrome MONDO:0007041
- Saethre-Chotzen syndrome MONDO:0007042
- Pfeiffer syndrome MONDO:0007043
- Jackson-Weiss syndrome MONDO:0007400
- Crouzon syndrome MONDO:0007405
- Beare-Stevenson cutis gyrata syndrome MONDO:0007412
- LADD syndrome 1 MONDO:0100302
- Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis MONDO:0020667
- familial scaphocephaly syndrome, McGillivray type MONDO:0012307
- bent bone dysplasia syndrome 1 MONDO:0013815
Drugs targeting this protein · 21
- INFIGRATINIB PHOSPHATE inhibitor
- INFIGRATINIB inhibitor
- REGORAFENIB inhibitor
- RG-1530 inhibitor
- LUCITANIB inhibitor
- BRIVANIB ALANINATE inhibitor
- ORANTINIB inhibitor
- NINTEDANIB ESYLATE inhibitor
- FEXAGRATINIB inhibitor
- ERDAFITINIB inhibitor
- E-7090 inhibitor
- FUTIBATINIB inhibitor
- BRIVANIB inhibitor
- LY-2874455 inhibitor
- FGFR INHIBITOR DEBIO 1347 inhibitor
- ROGARATINIB inhibitor
- TG100-801 inhibitor
- DERAZANTINIB inhibitor
- PEMIGATINIB inhibitor
- ENMD-981693 inhibitor
- XL-999 inhibitor
Neighborhood · nearest proteins
Related proteins · sequence + function similarity
- Fibroblast growth factor receptor 2 0.99
- Fibroblast growth factor receptor 2 0.99
- Fibroblast growth factor receptor 2 0.97
- Fibroblast growth factor receptor 2 0.97
- Fibroblast growth factor receptor 3 0.96
- Fibroblast growth factor receptor 2 0.96
- Fibroblast growth factor receptor 3 0.96
- Fibroblast growth factor receptor 2 0.96
- Fibroblast growth factor receptor 1 0.95
- Fibroblast growth factor receptor 1 0.95
- Fibroblast growth factor receptor 3 0.94
- Fibroblast growth factor receptor 3 0.94
Co-cited proteins · studied together in the literature
- Fibroblast growth factor 10 4 shared papers
- Serine/threonine-protein kinase PAK 4 1 shared papers
- Fibroblast growth factor 1 7 shared papers
- Fibroblast growth factor receptor 1 9 shared papers
- Fibroblast growth factor 8 4 shared papers
- E3 ubiquitin-protein ligase CBL 4 shared papers
- Fibroblast growth factor receptor 3 7 shared papers
- Fibroblast growth factor receptor 2 2 shared papers
- Fibroblast growth factor 2 4 shared papers
- Matrix metallopeptidase-21 1 shared papers
- Fibroblast growth factor receptor 4 6 shared papers
- 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 2 shared papers
Literature · 83 cited papers
- A human laterality disorder caused by a homozygous deleterious mutation in MMP21. J. Med. Genet. · 2015
- An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
- Bent bone dysplasia-FGFR2 type, a distinct skeletal disorder, has deficient canonical FGF signaling. Am. J. Hum. Genet. · 2012
- The Casitas B lineage lymphoma (Cbl) mutant G306E enhances osteogenic differentiation in human mesenchymal stromal cells in part by decreased Cbl-mediated platelet-derived growth factor receptor alpha and fibroblast growth factor receptor 2 ubiquitination. J. Biol. Chem. · 2011
- A novel mode of protein kinase inhibition exploiting hydrophobic motifs of autoinhibited kinases: discovery of ATP-independent inhibitors of fibroblast growth factor receptor. J. Biol. Chem. · 2011
- Fibroblast growth factor signalling: from development to cancer. Nat. Rev. Cancer · 2010
- Novel phosphotyrosine targets of FGFR2IIIb signaling. Cell. Signal. · 2009
- FGFR2 abnormalities underlie a spectrum of bone, skin, and cancer pathologies. J. Invest. Dermatol. · 2009
- Large-scale proteomics analysis of the human kinome. Mol. Cell. Proteomics · 2009
- Aberrant receptor internalization and enhanced FRS2-dependent signaling contribute to the transforming activity of the fibroblast growth factor receptor 2 IIIb C3 isoform. J. Biol. Chem. · 2009
- A crystallographic snapshot of tyrosine trans-phosphorylation in action. Proc. Natl. Acad. Sci. U.S.A. · 2008
- FGFR2-Cbl interaction in lipid rafts triggers attenuation of PI3K/Akt signaling and osteoblast survival. Bone · 2008
- … and 71 more in the literature graph