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Search results 1 to 32 out of 32 for Fgfr1

Category restricted to ProteinDomain (x)

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Categories

Category: ProteinDomain
Type Details Score
Protein Domain
Type: Domain
Description: Fibroblast growth factor receptor 1 (FGFR1) oncogene partner (FOP) is a centrosomal protein that is involved in anchoring microtubules to centrosomes. This domain includes a Lis-homology motif. It forms an α-helical bundle and is involved in dimerisation [].
Protein Domain
Type: Family
Description: This entry represents GRB2-associated-binding proteins 1-4 (Gab1-4) and similar proteins from animals. Proteins in this family contain one PH domain. GAB1 from humans and its orthologues dos and soc-1 from Drosophila and C. elegans [], respectively, function as adapter proteins that modulate intracellular signalling cascades triggered by activated receptor-type kinases. Gab1 from human plays a role in FGFR1 signalling, is involved in the MET/HGF-signalling pathway and functions as an important upstream regulator in EGF-mediated activation of mTORCs [, ].
Protein Domain
Type: Family
Description: Suppressor of IKBKE 1 (SIKE) is a physiological suppressor of IKK-epsilon and TBK1 []. IKKepsilon and TBK1 are two IKK-related kinases critically involved in virus- and TLR3-triggered activation of interferon regulatory factor 3 (IRF-3).Other members of this family are circulating cathodic antigen (CCA), found in Schistosoma mansoni (Blood fluke) [, ], and FGFR1 oncogene partner 2, which may be involved in wound healing pathway [].
Protein Domain
Type: Family
Description: Neuroplastin and basigin are members of the immunoglobulin (Ig) superfamily. They have two Ig domains that project into the extracellular space. They are also present as isoforms containing an additional N-terminal Ig domain. They contain a glutamate (E) at exactly the same position in the transmembrane domain, which may be important for molecular interactions within the membrane region [].Neuroplastin is a probable homophilic and heterophilic cell adhesion molecule involved in long term potentiation at hippocampal excitatory synapses through activation of p38MAPK []. It may also regulate neurite outgrowth by activating the FGFR1 signaling pathway []. It may play a role in synaptic plasticity [].
Protein Domain
Type: Family
Description: Fibroblast growth factors (FGFs) [, ]are a family of multifunctional proteins, often referred to as 'promiscuous growth factors' due to their diverse actions on multiple cell types [, ]. 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 [, , , , , ]. FGF involvement is critical during normal development of both vertebrates and invertebrates, and irregularities in their function leads to a range of developmental defects [, , , ]. 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 (β-trefoil topology) []. There are currently over 20 different FGF family members that have been identified in mammals, all of which are structurally related signaling molecules [, ]. They exert their effects through four distinct membrane fibroblast growth factor receptors (FGFRs), FGFR1 to FGFR4 [], which belong to the tyrosine kinase superfamily. Upon binding to FGF, the receptors dimerize and their intracellular tyrosine kinase domains become active [].This entry represents fibroblast growth factor 5 (FGF5). This protein plays an important role in the regulation of cell proliferation and cell differentiation. It is required for normal regulation of the hair growth cycle, as it functions as an inhibitor of hair elongation by promoting progression from anagen, the growth phase of the hair follicle, into catagen, the apoptosis-induced regression phase [, ]. FGF5 has a high affinity for FGFR1 and FGFR2 [].
Protein Domain
Type: Family
Description: Fibroblast growth factors (FGFs) [, ]are a family of multifunctional proteins, often referred to as 'promiscuous growth factors' due to their diverse actions on multiple cell types [, ]. 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 [, , , , , ]. FGF involvement is critical during normal development of both vertebrates and invertebrates, and irregularities in their function leads to a range of developmental defects [, , , ]. 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 (β-trefoil topology) []. There are currently over 20 different FGF family members that have been identified in mammals, all of which are structurally related signaling molecules [, ]. They exert their effects through four distinct membrane fibroblast growth factor receptors (FGFRs), FGFR1 to FGFR4 [], which belong to the tyrosine kinase superfamily. Upon binding to FGF, the receptors dimerize and their intracellular tyrosine kinase domains become active [].This entry represents fibroblast growth factor 3 (FGF3), also known as heparin-binding growth factor 3 and INT-2 proto-oncogene protein. The protein plays an important role in the regulation of embryonic development, cell proliferation and differentiation, and is required for normal ear development [, ]. FGF3 has a high affinity for FGFR3 and FGFR2, but a low affinity for FGFR1 [].
Protein Domain
Type: Domain
Description: Fibroblast growth factors (FGFs) [, ]are a family of multifunctional proteins, often referred to as 'promiscuous growth factors' due to their diverse actions on multiple cell types [, ]. 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 [, , , , , ]. FGF involvement is critical during normal development of both vertebrates and invertebrates, and irregularities in their function leads to a range of developmental defects [, , , ]. 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 (β-trefoil topology) []. There are currently over 20 different FGF family members that have been identified in mammals, all of which are structurally related signaling molecules [, ]. They exert their effects through four distinct membrane fibroblast growth factor receptors (FGFRs), FGFR1 to FGFR4 [], which belong to the tyrosine kinase superfamily. Upon binding to FGF, the receptors dimerize and their intracellular tyrosine kinase domains become active [].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 []. The three immunoglobin(Ig)-like domains, D1, D2, and D3, present a stretch of acidic amino acids (known 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 ligandaffinities and tissue distribution [, ]. 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 []. However, there are some exceptions. For example, FGF7 only interacts with FGFR2 []and FGF18 was recently shown to only activate FGFR3 []. Fibroblast growth factor receptor 1 (FGFR1) binds both acidic and basic fibroblast growth factors and is involved in limb induction []. FGFR1 has been shown to be associated with Pfeiffer syndrome [], and cleft lip and/or palate [, ]. Fibroblast growth factor receptor 1 has been shown to interact with growth factor receptor-bound protein 14 (GRB14) [], Src homology 2 domain containing adaptor protein B (SHB) [], fibroblast growth factor receptor substrate 2 (FRS2)[]and fibroblast growth factor 1 (FGF1) [, ].This entry represents the catalytic domain of FGFR1.
Protein Domain
Type: Family
Description: Fibroblast growth factors (FGFs) [, ]are a family of multifunctional proteins, often referred to as 'promiscuous growth factors' due to their diverse actions on multiple cell types [, ]. 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 [, , , , , ]. FGF involvement is critical during normal development of both vertebrates and invertebrates, and irregularities in their function leads to a range of developmental defects [, , , ]. 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 (β-trefoil topology) []. There are currently over 20 different FGF family members that have been identified in mammals, all of which are structurally related signaling molecules [, ]. They exert their effects through four distinct membrane fibroblast growth factor receptors (FGFRs), FGFR1 to FGFR4 [], which belong to the tyrosine kinase superfamily. Upon binding to FGF, the receptors dimerize and their intracellular tyrosine kinase domains become active [].
Protein Domain
Type: Family
Description: Fibroblast growth factors (FGFs) [, ]are a family of multifunctional proteins, often referred to as 'promiscuous growth factors' due to their diverse actions on multiple cell types [, ]. 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 [, , , , , ]. FGF involvement is critical during normal development of both vertebrates and invertebrates, and irregularities in their function leads to a range of developmental defects [, , , ]. 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 (β-trefoil topology) []. There are currently over 20 different FGF family members that have been identified in mammals, all of which are structurally related signaling molecules [, ]. They exert their effects through four distinct membrane fibroblast growth factor receptors (FGFRs), FGFR1 to FGFR4 [], which belong to the tyrosine kinase superfamily. Upon binding to FGF, the receptors dimerize and their intracellular tyrosine kinase domains become active [].This entry represents fibroblast growth factor 18 (FGF18), also referred to ZFGF5. FGF18 is required for normal ossification and bone development and stimulates hepatic and intestinal proliferation [, , , ].
Protein Domain
Type: Family
Description: Fibroblast growth factors (FGFs) [, ]are a family of multifunctional proteins, often referred to as 'promiscuous growth factors' due to their diverse actions on multiple cell types [, ]. 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 [, , , , , ]. FGF involvement is critical during normal development of both vertebrates and invertebrates, and irregularities in their function leads to a range of developmental defects [, , , ]. 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 (β-trefoil topology) []. There are currently over 20 different FGF family members that have been identified in mammals, all of which are structurally related signaling molecules [, ]. They exert their effects through four distinct membrane fibroblast growth factor receptors (FGFRs), FGFR1 to FGFR4 [], which belong to the tyrosine kinase superfamily. Upon binding to FGF, the receptors dimerize and their intracellular tyrosine kinase domains become active [].This entry represents fibroblast growth factor 11 (FGF11), also known as fibroblast growth factor homologous factor 3. It currently has no known function, but it is thought to be involved in nervous system development and function [].
Protein Domain
Type: Family
Description: Fibroblast growth factors (FGFs) [, ]are a family of multifunctional proteins, often referred to as 'promiscuous growth factors' due to their diverse actions on multiple cell types [, ]. 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 [, , , , , ]. FGF involvement is critical during normal development of both vertebrates and invertebrates, and irregularities in their function leads to a range of developmental defects [, , , ]. 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 (β-trefoil topology) []. There are currently over 20 different FGF family members that have been identified in mammals, all of which are structurally related signaling molecules [, ]. They exert their effects through four distinct membrane fibroblast growth factor receptors (FGFRs), FGFR1 to FGFR4 [], which belong to the tyrosine kinase superfamily. Upon binding to FGF, the receptors dimerize and their intracellular tyrosine kinase domains become active [].This entry represents fibroblast growth factor 22 (FGF22), which plays a role in the fasting response, glucose homeostasis, lipolysis and lipogenesis, and has been shown to stimulate cell proliferation in vitro [, ]. FGF22 is expressed in skin, with low expression found in brain. In mouse FGF22 is preferentially expressed in the inner root sheath of the hair follicle, which suggests a role in hair development [].
Protein Domain
Type: Family
Description: Fibroblast growth factors (FGFs) [, ]are a family of multifunctional proteins, often referred to as 'promiscuous growth factors' due to their diverse actions on multiple cell types [, ]. 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 [, , , , , ]. FGF involvement is critical during normal development of both vertebrates and invertebrates, and irregularities in their function leads to a range of developmental defects [, , , ]. 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 (β-trefoil topology) []. There are currently over 20 different FGF family members that have been identified in mammals, all of which are structurally related signaling molecules [, ]. They exert their effects through four distinct membrane fibroblast growth factor receptors (FGFRs), FGFR1 to FGFR4 [], which belong to the tyrosine kinase superfamily. Upon binding to FGF, the receptors dimerize and their intracellular tyrosine kinase domains become active [].This entry represents fibroblast growth factor 21 (FGF21), which stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression []. FGF21 has been shown to protect animals from diet-induced obesity when overexpressed in transgenic mice. It also lowers blood glucose and triglyceride levels when administered to diabetic rodents [], suggesting it may exhibit the therapeutic characteristics necessary for effective treatment of diabetes. Treatment of animals with FGF21 results in increased energy expenditure, fat utilisation and lipid excretion []. FGF21 is most abundantly expressed in the liver, and also expressed in the thymus at lower levels [].
Protein Domain
Type: Family
Description: Fibroblast growth factors (FGFs) [, ]are a family of multifunctional proteins, often referred to as 'promiscuous growth factors' due to their diverse actions on multiple cell types [, ]. 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 [, , , , , ]. FGF involvement is critical during normal development of both vertebrates and invertebrates, and irregularities in their function leads to a range of developmental defects [, , , ]. 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 (β-trefoil topology) []. There are currently over 20 different FGF family members that have been identified in mammals, all of which are structurally related signaling molecules [, ]. They exert their effects through four distinct membrane fibroblast growth factor receptors (FGFRs), FGFR1 to FGFR4 [], which belong to the tyrosine kinase superfamily. Upon binding to FGF, the receptors dimerize and their intracellular tyrosine kinase domains become active [].This entry represents fibroblast growth factor 16 (FGF16). The protein plays an important role in the regulation of embryonic development, cell proliferation and cell differentiation, and is required for normal cardiomyocyte proliferation and heart development []. In rat embryos, FGF16 is detected predominantly in brown adipose tissue, where it shows significant mitogenic activity for primary brown adipocytes, mediated by activation of FGFR4 [].
Protein Domain
Type: Family
Description: Fibroblast growth factors (FGFs) [, ]are a family of multifunctional proteins, often referred to as 'promiscuous growth factors' due to their diverse actions on multiple cell types [, ]. 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 [, , , , , ]. FGF involvement is critical during normal development of both vertebrates and invertebrates, and irregularities in their function leads to a range of developmental defects [, , , ]. 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 (β-trefoil topology) []. There are currently over 20 different FGF family members that have been identified in mammals, all of which are structurally related signaling molecules [, ]. They exert their effects through four distinct membrane fibroblast growth factor receptors (FGFRs), FGFR1 to FGFR4 [], which belong to the tyrosine kinase superfamily. Upon binding to FGF, the receptors dimerize and their intracellular tyrosine kinase domains become active [].This entry represents fibroblast growth factor 17 (FGF17). The protein plays an important role in the regulation of embryonic development and in the induction and patterning of the embryonic brain. It is required for normal brain development []. In mouse, FGF17 is localised to specific sites in the brain, the developing skeleton and developing arteries, which suggests a role in central nervous system, bone and vascular growth [, , ].
Protein Domain
Type: Family
Description: Fibroblast growth factors (FGFs) [, ]are a family of multifunctional proteins, often referred to as 'promiscuous growth factors' due to their diverse actions on multiple cell types [, ]. 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 [, , , , , ]. FGF involvement is critical during normal development of both vertebrates and invertebrates, andirregularities in their function leads to a range of developmental defects [, , , ]. 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 (β-trefoil topology) []. There are currently over 20 different FGF family members that have been identified in mammals, all of which are structurally related signaling molecules [, ]. They exert their effects through four distinct membrane fibroblast growth factor receptors (FGFRs), FGFR1 to FGFR4 [], which belong to the tyrosine kinase superfamily. Upon binding to FGF, the receptors dimerize and their intracellular tyrosine kinase domains become active [].This entry represents fibroblast growth factor 14 (FGF14), also known as fibroblast growth factor homologous factor 4. In mouse, FGF14 is widely expressed in the brain, spinal cord, major arteries and thymus []. The protein is involved in neuronal development and function. FGF14-deficient mice suffer from severe ataxia and other neurological deficits []. Defects in the human FGF14 gene cause Spinocerebellar ataxia, characterised by ataxia with tremor, orofacial dyskinesia, psychiatric symptoms and cognitive deficits [].
Protein Domain
Type: Family
Description: Fibroblast growth factors (FGFs) [, ]are a family of multifunctional proteins, often referred to as 'promiscuous growth factors' due to their diverse actions on multiple cell types [, ]. 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 [, , , , , ]. FGF involvement is critical during normal development of both vertebrates and invertebrates, and irregularities in their function leads to a range of developmental defects [, , , ]. 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 (β-trefoil topology) []. There are currently over 20 different FGF family members that have been identified in mammals, all of which are structurally related signaling molecules [, ]. They exert their effects through four distinct membrane fibroblast growth factor receptors (FGFRs), FGFR1 to FGFR4 [], which belong to the tyrosine kinase superfamily. Upon binding to FGF, the receptors dimerize and their intracellular tyrosine kinase domains become active [].This entry represents fibroblast growth factor 20 (FGF20). It is involved in embryonic development, cell growth, morphogenesis, tissue repair, and tumour growth and invasion [, , ]. FGF20 is expressed in normal brain, particularly the cerebellum [], and has been shown to enhance the survival of midbrain dopaminergic neurons in vitro [].
Protein Domain
Type: Family
Description: Fibroblast growth factors (FGFs) [, ]are a family of multifunctional proteins, often referred to as 'promiscuous growth factors' due to their diverse actions on multiple cell types [, ]. 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 [, , , , , ]. FGF involvement is critical during normal development of both vertebrates and invertebrates, and irregularities in their function leads to a range of developmental defects [, , , ]. 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 (β-trefoil topology) []. There are currently over 20 different FGF family members that have been identified in mammals, all of which are structurally related signaling molecules [, ]. They exert their effects through four distinct membrane fibroblast growth factor receptors (FGFRs), FGFR1 to FGFR4 [], which belong to the tyrosine kinase superfamily. Upon binding to FGF, the receptors dimerize and their intracellular tyrosine kinase domains become active [].This entry represents fibroblast growth factor 13 (FGF13), also known as fibroblast growth factor homologous factor 2. It is thought to be involved in nervous system development and function []. FGF13 has been shown to induce cell growth of lung fibroblasts and aortic smooth muscle cells, but has no effect on dermal vascular endothelial cells []. It also is thought to regulate voltage-gated sodium channels transport and function, and play a role in MAPK signaling []. The localisation and tissue-specific expression pattern of FGF13 has made it a possible candidate for familial cases of Borjeson-Forssman-Lehmann syndrome (BFLS) and other syndromal and nonspecific forms of X-linked mental retardation [].
Protein Domain
Type: Family
Description: Fibroblast growth factors (FGFs) [, ]are a family of multifunctional proteins, often referred to as 'promiscuous growth factors' due to their diverse actions on multiple cell types [, ]. 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 [, , , , , ]. FGF involvement is critical during normal development of both vertebrates and invertebrates, and irregularities in their function leads to a range of developmental defects [, , , ]. 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 (β-trefoil topology) []. There are currently over 20 different FGF family members that have been identified in mammals, all of which are structurally related signaling molecules [, ]. They exert their effects through four distinct membrane fibroblast growth factor receptors (FGFRs), FGFR1 to FGFR4 [], which belong to the tyrosine kinase superfamily. Upon binding to FGF, the receptors dimerize and their intracellular tyrosine kinase domains become active [].This entry represents fibroblast growth factor 23 (FGF23), which is secreted by osteoblasts and osteoclasts []. FGF23 acts on kidneys, where it decreases the expression of NPT2, a sodium-phosphate cotransporter in the proximal tubule []. FGF23 is responsible for phosphate metabolism, decreasing the reabsorption and increasing excretion of phosphate []. FGF23 is involved in the pathogenesis of three hypophosphatemic disorders; oncogenic osteomalacia (OOM), X-linked hypophosphatemia (XLH) and autosomal dominant hypophosphatemic rickets (ADHR). These conditions are characterised by hypophosphatemia, decreased renal phosphate reabsorption, normal or low serum calcitriol concentrations and defective skeletal mineralisation [, , ].
Protein Domain
Type: Family
Description: Fibroblast growth factors (FGFs) [, ]are a family of multifunctional proteins, often referred to as 'promiscuous growth factors' due to their diverse actions on multiple cell types [, ]. 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 [, , , , , ]. FGF involvement is critical during normal development of both vertebrates and invertebrates, and irregularities in their function leads to a range of developmental defects [, , , ]. 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 (β-trefoil topology) []. There are currently over 20 different FGF family members that have been identified in mammals, all of which are structurally related signaling molecules [, ]. They exert their effects through four distinct membrane fibroblast growth factor receptors (FGFRs), FGFR1 to FGFR4 [], which belong to the tyrosine kinase superfamily. Upon binding to FGF, the receptors dimerize and their intracellular tyrosine kinase domains become active [].This entry represents fibroblast growth factor 1 (FGF1), also known as heparin-binding growth factor 1 and acidic fibroblast growth factor. The protein functions as a modifier of endothelial cell migration and proliferation, as well as an angiogenic factor. It acts as a mitogen for a variety of mesoderm- and neuroectoderm-derived cells in vitro, and is therefore thought to be involved in organogenesis [, , ]. In addition to interacting with FGFR1-4, FGF1 has also been shown to interact with casein kinase II subunits [], heat shock proteins []and acidic fibroblast growth factor intracellular-binding protein [].
Protein Domain
Type: Family
Description: Fibroblast growth factors (FGFs) [, ]are a family of multifunctional proteins, often referred to as 'promiscuous growth factors' due to their diverse actions on multiple cell types [, ]. 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 [, , , , , ]. FGF involvement is critical during normal development of both vertebrates and invertebrates, and irregularities in their function leads to a range of developmental defects [, , , ]. 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 (β-trefoil topology) []. There are currently over 20 different FGF family members that have been identified in mammals, all of which are structurally related signaling molecules [, ]. They exert their effects through four distinct membrane fibroblast growth factor receptors (FGFRs), FGFR1 to FGFR4 [], which belong to the tyrosine kinase superfamily. Upon binding to FGF, the receptors dimerize and their intracellular tyrosine kinase domains become active [].This entry represents fibroblast growth factor 10 (FGF10), also known as keratinocyte growth factor 2. This protein plays an important role in the regulation of embryonic development, cell proliferation, cell differentiation and cell migration. FGF10 exhibits mitogenic activity for keratinizing epidermal cells, but essentially no activity for fibroblasts, which is similar to the biological activity of FGF7 []. Studies suggest FGF10 is required for embryonic epidermal morphogenesis including brain development, lung morphogenesis, and initiation of limb bud formation [, , ]. FGF10 is also implicated as a primary factor in the process of wound healing [, ]. FGF10 interacts with FGFR1, but has a higher affinity FGFR2 [, ].
Protein Domain
Type: Family
Description: Fibroblast growth factors (FGFs) [, ]are a family of multifunctional proteins, often referred to as 'promiscuous growth factors' due to their diverse actions on multiple cell types [, ]. 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 [, , , , , ]. FGF involvement is critical during normal development of both vertebrates and invertebrates, and irregularities in their function leads to a range of developmental defects [, , , ]. 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 (β-trefoil topology) []. There are currently over 20 different FGF family members that have been identified in mammals, all of which are structurally related signaling molecules [, ]. They exert their effects through four distinct membrane fibroblast growth factor receptors (FGFRs), FGFR1 to FGFR4 [], which belong to the tyrosine kinase superfamily. Upon binding to FGF, the receptors dimerize and their intracellular tyrosine kinase domains become active [].This entry represents fibroblast growth factor 12 (FGF12), also known as fibroblast growth factor homologous factor 1. It lacks the N-terminal signal sequence present in most of the FGF family members, but it contains clusters of basic residues that have been demonstrated to act as a nuclear localisation signal. When transfected into mammalian cells, it accumulates in the nucleus, but is not secreted []. Although it currently has no known function, it is thought to be involved in nervous system development and function [, ].
Protein Domain
Type: Family
Description: Fibroblast growth factors (FGFs) [, ]are a family of multifunctional proteins, often referred to as 'promiscuous growth factors' due to their diverse actions on multiple cell types [, ]. 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 [, , , , , ]. FGF involvement is critical during normal development of both vertebrates and invertebrates, and irregularities in their function leads to a range of developmental defects [, , , ]. 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 (β-trefoil topology) []. There are currently over 20 different FGF family members that have been identified in mammals, all of which are structurally related signaling molecules [, ]. They exert their effects through four distinct membrane fibroblast growth factor receptors (FGFRs), FGFR1 to FGFR4 [], which belong to the tyrosine kinase superfamily. Upon binding to FGF, the receptors dimerize and their intracellular tyrosine kinase domains become active [].This entry represents fibroblast growth factor 9 (FGF9), also known as glia-activating factor and heparin-binding growth factor 9. This protein plays an important role in the regulation of embryonic development, cell proliferation, cell differentiation and cell migration. It is involved in cyclic proliferation of uterine endometrial stroma []and can act as both a paracrine mitogen for epithelial cells and an autocrine mitogen for stromal cells []. FGF9 has also been shown to play a vital role in male development, as it is needed to carry out important masculinising developmental functions, such testicular embryogenesis [, ]. FGF9 Interacts with FGFR1, FGFR2, FGFR3 and FGFR4, but has highest affinity for FGFR3 [, ].
Protein Domain
Type: Family
Description: Fibroblast growth factors (FGFs) [, ]are a family of multifunctional proteins, often referred to as 'promiscuous growth factors' due to their diverse actions on multiple cell types [, ]. 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 [, , , , , ]. FGF involvement is critical during normal development of both vertebrates and invertebrates, and irregularities in their function leads to a range of developmental defects [, , , ]. 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 (β-trefoil topology) []. There are currently over 20 different FGF family members that have been identified in mammals, all of which are structurally related signaling molecules [, ]. They exert their effects through four distinct membrane fibroblast growth factor receptors (FGFRs), FGFR1 to FGFR4 [], which belong to the tyrosine kinase superfamily. Upon binding to FGF, the receptors dimerize and their intracellular tyrosine kinase domains become active [].This entry represents fibroblast growth factor 6 (FGF6). This protein plays an important role in the regulation of cell proliferation, cell differentiation, angiogenesis and myogenesis, and is required for normal muscle regeneration [, , ]. It may also regulate bone metabolism, as shown by its activity on both osteoblasts and osteoclasts []. FGF6 has a high affinity for FGFR1, FGFR2 and FGFR4 [].
Protein Domain
Type: Family
Description: Fibroblast growth factors (FGFs) [, ]are a family of multifunctional proteins, often referred to as 'promiscuous growth factors' due to their diverse actions on multiple cell types [, ]. 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 [, , , , , ]. FGF involvement is critical during normal development of both vertebrates and invertebrates, and irregularities in their function leads to a range of developmental defects [, , , ]. 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 (β-trefoil topology) []. There are currently over 20 different FGF family members that have been identified in mammals, all of which are structurally related signaling molecules [, ]. They exert their effects through four distinct membrane fibroblast growth factor receptors (FGFRs), FGFR1 to FGFR4 [], which belong to the tyrosine kinase superfamily. Upon binding to FGF, the receptors dimerize and their intracellular tyrosine kinase domains become active [].This entry represents fibroblast growth factor 8 (FGF8), also known as androgen-induced growth factor. It plays an important role in the regulation of embryonic development, cell proliferation, cell differentiation and cell migration. FGF8 is also required for normal brain, eye, ear and limb development during embryogenesis, and is required for normal development of the gonadotropin-releasing hormone (GnRH) neuronal system [, , , , ]. Fibroblast growth factor 8 also supports androgen and anchorage independent growth of mammary tumor cells []. FGF8 has an affinity for the all the growth factor receptors, but has the highest affinity with FGFR3 and FGFR4 [, ].This entry also includes the orthologous Fibroblast growth factor 8b from zebrafish.
Protein Domain
Type: Family
Description: Fibroblast growth factors (FGFs) [, ]are a family of multifunctional proteins, often referred to as 'promiscuous growth factors' due to their diverse actions on multiple cell types [, ]. 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 [, , , , , ]. FGF involvement is critical during normal development of both vertebrates and invertebrates, and irregularities in their function leads to a range of developmental defects [, , , ]. 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 (β-trefoil topology) []. There are currently over 20 different FGF family members that have been identified in mammals, all of which are structurally related signaling molecules [, ]. They exert their effects through four distinct membrane fibroblast growth factor receptors (FGFRs), FGFR1 to FGFR4 [], which belong to the tyrosine kinase superfamily. Upon binding to FGF, the receptors dimerize and their intracellular tyrosine kinase domains become active [].This entry represents fibroblast growth factor 7 (FGF7), also known as keratinocyte growth factor (KGF). This protein plays an important role in the regulation of embryonic development, cell proliferation and cell differentiation. It is a potent epithelial cell-specific growth factor, whose mitogenic activity is predominantly exhibited in keratinocytes, but not in fibroblasts and endothelial cells []. Studies of mouse and rat have implicated FGF7 in morphogenesis of epithelium, wound repair, hair development and early lung organogenesis [, , , ]. FGF7 has a high affinity for FGFR2 and has also been shown to interact with various collagens []and heparan sulfate proteoglycan 2 (perlecan) [].
Protein Domain
Type: Family
Description: Fibroblast growth factors (FGFs) [, ]are a family of multifunctional proteins, often referred to as 'promiscuous growth factors' due to their diverse actions on multiple cell types [, ]. 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 [, , , , , ]. FGF involvement is critical during normal development of both vertebrates and invertebrates, and irregularities in their function leads to a range of developmental defects [, , , ]. 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 (β-trefoil topology) []. There are currently over 20 different FGF family members that have been identified in mammals, all of which are structurally related signaling molecules [, ]. They exert their effects through four distinct membrane fibroblast growth factor receptors (FGFRs), FGFR1 to FGFR4 [], which belong to the tyrosine kinase superfamily. Upon binding to FGF, the receptors dimerize and their intracellular tyrosine kinase domains become active [].This entry represents fibroblast growth factor 4 (FGF4), also known as heparin secretory transforming protein 1. This protein plays an important role in the regulation of embryonic development, cell proliferation and differentiation []. Studies on the mouse protein suggest a function in bone morphogenesis and limb development through the sonic hedgehog (SHH) signaling pathway [, ].
Protein Domain
Type: Family
Description: Fibroblast growth factors (FGFs) [, ]are a family of multifunctional proteins, often referred to as 'promiscuousgrowth factors' due to their diverse actions on multiple cell types [, ]. 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 [, , , , , ]. FGF involvement is critical during normal development of both vertebrates and invertebrates, and irregularities in their function leads to a range of developmental defects [, , , ]. 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 (β-trefoil topology) []. There are currently over 20 different FGF family members that have been identified in mammals, all of which are structurally related signaling molecules [, ]. They exert their effects through four distinct membrane fibroblast growth factor receptors (FGFRs), FGFR1 to FGFR4 [], which belong to the tyrosine kinase superfamily. Upon binding to FGF, the receptors dimerize and their intracellular tyrosine kinase domains become active [].This entry represents fibroblast growth factor 2 (FGF2), also known as heparin-binding growth factor 2 and basic fibroblast growth factor. The protein plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration and is a potent mitogen in vitro [, ]. FGF2 has a high affinity for FGFR1, FGFR2 and FGFR4, but a very low affinity with FGFR3 [, , , ]. FGF2 has also been shown to interact with casein kinase II subunit alpha []and some ribosomal proteins [, ].
Protein Domain
Type: Domain
Description: This entry represents the C-terminal SH2 domain of phosphatidylinositol-4, 5-bisphosphate phosphodiesterase gamma (PLC-gamma).PLC-gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLC-gamma is composed of a pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases []. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLC-gamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium []. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated site [].
Protein Domain
Type: Domain
Description: This entry represents the N-terminal SH2 domain of phosphatidylinositol-4, 5-bisphosphate phosphodiesterase gamma (PLC-gamma).PLC-gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLC-gamma is composed of a pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases []. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLC-gamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium []. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated site [].
Protein Domain
Type: Family
Description: Fibroblast growth factors (FGFs) [, ]are a family of multifunctional proteins, often referred to as 'promiscuous growth factors' due to their diverse actions on multiple cell types [, ]. 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 [, , , , , ]. FGF involvement is critical during normal development of both vertebrates and invertebrates, and irregularities in their function leads to a range of developmental defects [, , , ]. 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 (β-trefoil topology) []. There are currently over 20 different FGF family members that have been identified in mammals, all of which are structurally related signaling molecules [, ]. They exert their effects through four distinct membrane fibroblast growth factor receptors (FGFRs), FGFR1 to FGFR4 [], which belong to the tyrosine kinase superfamily. Upon binding to FGF, the receptors dimerize and their intracellular tyrosine kinase domains become active [].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 []. The three immunoglobin(Ig)-like domains, D1, D2, and D3, present a stretch of acidic amino acids (known 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 [, ]. 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 []. However, there are some exceptions. For example, FGF7 only interacts with FGFR2 []and FGF18 was recently shown to only activate FGFR3 []. This entry represents the fibroblast growth factor receptor family.
Protein Domain
Type: Family
Description: Neuroplastin and basigin are members of the immunoglobulin (Ig) superfamily. They have two Ig domains that project into the extracellular space. They are also present as isoforms containing an additional N-terminal Ig domain. They contain a glutamate (E) at exactly the same position in the transmembrane domain, which may be important for molecular interactions within the membrane region [].Basigin is present on the surface of tumour cells and stimulate nearby fibroblasts to synthesise matrix metalloproteases (MMPs), which play an important role in tumour invasiveness and metastasis []. Basigin has also been repeatedly implicated in the proper function of the blood brain barrier [, ]. In addition, the protein is essential for fertility in both males and females[]. In males, it is required for the completion of spermatogenesis, while in females, it is needed for maintaining normal reproductive functions. Basigins are highly glycosylated membrane proteins, the degree of glycosylation varying with tissue type. The extracellular region of basigin contains two randomly arranged Ig domains: an Ig-like C2-type domain and an Ig-like V-domain [].Neuroplastin is a probable homophilic and heterophilic cell adhesion molecule involved in long term potentiation at hippocampal excitatory synapses through activation of p38MAPK []. It may also regulate neurite outgrowth by activating the FGFR1 signaling pathway []. It may play a role in synaptic plasticity [].Contactins are cell adhesion molecules that belong to the immunoglobulin superfamily and are involved in neural development []. Contactin-2 (CNTN2/axonin-1/TAG-1/TAX-1) is highly expressed at the axon growth cone and plays an important role in regulating axon guidance and path finding, as well as in neuron migration. Contactin-6 (CNTN6/NB-3) binds Notch and and promotes oligodendrogliogenesis from progenitor cells and differentiation of oligodendrocyte precursor cells.Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays a role in axon guidance, self-avoidance and synaptic formation []. DSCAM is one of the largest Immunoglobulin (Ig) superfamily CAMs [], and contributes to defects in the central nervous system in Down syndrome patients [].This entry represents a family of neuronal cell adhesion molecules that belong to the immunoglobulin superfamily and are involved in neural development.
Protein Domain
Type: Family
Description: Fibroblast growth factors (FGFs) [, ]are a family of multifunctional proteins, often referred to as 'promiscuous growth factors' due to their diverse actions on multiple cell types [, ]. 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 [, , , , , ]. FGF involvement is critical during normal development of both vertebrates and invertebrates, and irregularities in their function leads to a range of developmental defects [, , , ]. 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 (β-trefoil topology) []. There are currently over 20 different FGF family members that have been identified in mammals, all of which are structurally related signaling molecules [, ]. They exert their effects through four distinct membrane fibroblast growth factor receptors (FGFRs), FGFR1 to FGFR4 [], which belong to the tyrosine kinase superfamily. Upon binding to FGF, the receptors dimerize and their intracellular tyrosine kinase domains become active [].Fibroblast growth factor 15 (FGF15) plays a key role in enterohepatic signaling, regulation of liver bile acid biosynthesis, gallbladder motility and metabolic homeostasis [, , ]. Mouse FGF15 has been shown to be stimulated when bile acids bind to farnesoid X receptor (FXR) [], and is therefore thought to a factor in chronic bile acid diarrhoea and in certain metabolic disorders [].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 [, ]. 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 distantcells. FGF signaling through the FGF receptors is also different, as they require klotho protein cofactors rather than heparin sulfate proteoglycan [].Fibroblast growth factor 19 (FGF19) plays a key role in enterohepatic signaling, regulation of liver bile acid biosynthesis, gallbladder motility and metabolic homeostasis [, , ]. 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 []. The protein is thought to be a factor in chronic bile acid diarrhoea and in certain metabolic disorders [, ]. 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 [, ]. 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 []. Unlike other members of the family that can bind several FGF receptors, FGF19 is specific for FGFR4 [].