Family

Fibroblast growth factor 15/19 (IPR028303)

Short name: FGF15/FGF19

Overlapping homologous superfamilies

Family relationships

Description

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]. FGFs are mitogens, which stimulate growth or differentiation of cells of mesodermal or neuroectodermal origin. 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. FGFs have internal pseudo-threefold symmetry (beta-trefoil topology) [PMID: 10830168]. 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. Upon binding to FGF, the receptors dimerize and their intracellular tyrosine kinase domains become active [PMID: 7583099].

Fibroblast growth factor 15 (FGF15) plays a key role in enterohepatic signaling, regulation of liver bile acid biosynthesis, gallbladder motility and metabolic homeostasis [PMID: 22302876, PMID: 16213224, PMID: 22396169]. Mouse FGF15 has been shown to be stimulated when bile acids bind to farnesoid X receptor (FXR) [PMID: 16213224], and is therefore thought to a factor in chronic bile acid diarrhoea and in certain metabolic disorders [PMID: 17823457].

FGF15 has been experimentally characterised in mouse, but has not been found in other species. However, there is an orthologous human protein, FGF19, and together they share about 50% amino acid identity and display similar endocrine functions, so are often referred to as FGF15/19 [PMID: 22396169, PMID: 22302876]. FGF15 and FGF19 differ from other FGFs due to subtle changes in their tertiary structure, they have low heparin binding affinity enabling them to diffuse away from their site of secretion and signal to distant cells. FGF signaling through the FGF receptors is also different, as they require klotho protein cofactors rather than heparin sulfate proteoglycan [PMID: 22396169].

Fibroblast growth factor 19 (FGF19) plays a key role in enterohepatic signaling, regulation of liver bile acid biosynthesis, gallbladder motility and metabolic homeostasis [PMID: 22302876, PMID: 16213224, PMID: 22396169]. Human FGF19 expression has been shown to be stimulated approximately 300-fold by physiological concentrations of bile acids including chenodeoxycholic acid, glycochenodeoxycholic acid and obeticholic acid in explants of ileal mucosa [PMID: 23518683]. The protein is thought to be a factor in chronic bile acid diarrhoea and in certain metabolic disorders [PMID: 22396169, PMID: 21436455].

FGF19 has been experimentally characterised in humans and other species, but has not been found in mouse. However there is an orthologous mouse protein, FGF15, and together they share about 50% amino acid identity and display similar endocrine functions, so are often referred to as FGF15/19 [PMID: 22396169, PMID: 22302876]. FGF15 and FGF19 differ from other FGFs due to subtle changes in their tertiary structure. They have low heparin binding affinity, enabling them to diffuse away from their site of secretion and signal to distant cells. FGF signaling through the FGF receptors is also different, as they require klotho protein cofactors rather than heparin sulfate proteoglycan [PMID: 22396169]. Unlike other members of the family that can bind several FGF receptors, FGF19 is specific for FGFR4 [PMID: 10525310].

GO terms

Biological Process

GO:0008543 fibroblast growth factor receptor signaling pathway

Molecular Function

GO:0005104 fibroblast growth factor receptor binding

Cellular Component

GO:0005576 extracellular region

Contributing signatures

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