Fibroblast growth factor receptor 2 (IPR028175)

Short name: FGF_rcpt_2

Family relationships


Fibroblast growth factors (FGFs) [PMID: 2549857, PMID: 3072709] are a family of multifunctional proteins, often referred to as 'promiscuous growth factors' due to their diverse actions on multiple cell types [PMID: 1705486, PMID: 8760337]. The function of FGFs in developmental processes include mesoderm induction, anterior-posterior patterning, limb development, and neural induction and development. In mature tissues, they are involved in diverse processes including keratinocyte organisation and wound healing [PMID: 11276432, PMID: 23000357, PMID: 15689573, PMID: 10441498, PMID: 23108135, PMID: 23016864]. FGF involvement is critical during normal development of both vertebrates and invertebrates, and irregularities in their function leads to a range of developmental defects [PMID: 1649700, PMID: 11746231, PMID: 14745970, PMID: 8978613]. Fibroblast growth factors are heparin-binding proteins and interactions with cell-surface-associated heparan sulfate proteoglycans have been shown to be essential for FGF signal transduction. There are currently over 20 different FGF family members that have been identified in mammals, all of which are structurally related signaling molecules [PMID: 8652550, PMID: 11276432]. They exert their effects through four distinct membrane fibroblast growth factor receptors (FGFRs), FGFR1 to FGFR4 [PMID: 7583099], which belong to the tyrosine kinase superfamily.

The FGFRs consist of an extracellular ligand-binding domain composed of three immunoglobulin-like domains (D1-D3), a single transmembrane helix domain, and an intracellular domain with tyrosine kinase activity [PMID: 18216218]. The three immunoglobin(Ig)-like domains, D1, D2, and D3, present a stretch of acidic amino acids (knonw as the acid box) between D1 and D2. This acid box can participate in the regulation of FGF binding to the FGFR. Immunoglobulin-like domains D2 and D3 are sufficient for FGF binding. FGFR family members differ from one another in their ligand affinities and tissue distribution [PMID: 16597617, PMID: 9212826]. Most FGFs can bind to several different FGFR subtypes. Indeed, FGF1 is sometimes referred to as the universal ligand, as it is capable of activating all of the different FGFRs [PMID: 8663044]. However, there are some exceptions. For example, FGF7 only interacts with FGFR2 [PMID: 16829530] and FGF18 was recently shown to only activate FGFR3 [PMID: 15781473].

This entry represents the fibroblast growth factor receptor 2 (previously known as keratinocyte growth factor receptor). Different splice variants of the receptor display high-affinity for acidic or basic fibroblast growth factors and/or keratinocyte growth factor, depending on the isoform [PMID: 8663044]. Mutations of FRFR2 are associated with numerous medical conditions that include abnormal bone development, such as craniosynostosis syndromes, and cancer [PMID: 17529973, PMID: 7987400, PMID: 20301628].

GO terms

Biological Process

GO:0048701 embryonic cranial skeleton morphogenesis

Molecular Function

GO:0005007 fibroblast growth factor-activated receptor activity

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.