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Fibroblast Growth Factor (FGF) Family
What is FGF?
FGF, also known as fibroblast growth factor, represents a family of approximately two dozen heparin-binding proteins that play pivotal roles in numerous cellular processes related to development and repair of tissues including brain, skin, and lungs.
FGFs function by binding to and activating high-affinity FGF receptors (FGFR) on target cells, causing a signal transduction cascade involving kinases and transcription factors. Activation of signaling pathways by fibroblast growth factors results in cellular effects such as mitogenesis, differentiation, migration, angiogenesis, and wound healing.
Biochemical properties of fibroblast growth factors
FGFs are medium sized single-chain proteins with molecular weights ranging from 15–25 kDa possessing a conserved core of about 120 amino acids. Originally two biochemical classes of fibroblast growth factor, acidic (FGF-1) and basic (FGF-2) were identified based on their isoelectric points (pI); now seven subfamilies are recognized based on sequence homology.
Applications of FGFs in biomedical research
Recombinant proteins from the FGF family are used in numerous cell culture applications. FGFs are important for maintaining, expanding and differentiating diverse types of cells in culture. FGF recombinant proteins are also employed to determine signaling interactions and pathways. For example:
- FGF-basic: maintenance of pluripotent stem cells
- FGF-10: differentiation of human pluripotent stem cells to insulin-producing pancreatic-like cells
- FGF-7/KGF: expansion of neural stem and progenitor cells
- FGF-6: study of pathways involved in muscle development
Functions of fibroblast growth factors
Proteins in the FGF family share the functional abilities to signal through at least one of four tyrosine kinase receptors (FGFR1 through FGFR4) and interact with heparin sulphate proteoglycans (HSPGs).
FGF function varies depending on the type of receptor engaged as well as target cell location and phenotype. The chart below lists the known receptors, target cells, and functions of each member of the FGF family.
| FGF name/type | Target cells (partial list) | FGF receptor(s) | FGF function(s) (partial list) |
|---|---|---|---|
| FGF1 (Acidic FGF) Heparin-Binding Growth Factor-1 (HBGF-1) ECGF-beta (Endothelial Cell Growth Factor-beta) | mesenchymal, neuroectodermal endothelial cells | all FGF receptors | Angiogenic in vivo, mitogenic in in vitro, wound healing |
| FGF2 (Basic FGF) Heparin-Binding Growth Factor-2 (HBGF-2) Prostatropin | mesenchymal, neuroectodermal endothelial cells | 1b, 1c, 2c, 3c, 4 | Vasculogenesis, wound healing, angiogenesis, hematopoiesis, neuron survival |
| FGF3 int-2 | epithelial cells that express FGF receptor 2b | 2b | Mesoderm induction, angiogenesis, inner ear development |
| FGF4 Heparin Secretory Transforming protein (HST-1) Transforming protein KS3 Heparin-Binding Growth Factor-4 (HBGF-4) | cells that express FGF receptors | 1c, 2c, 3c, 4 | Angiogenesis, vertebrate limb development and development of stomach cancer |
| FGF5 Heparin-Binding Growth Factor-5 (HBGF-5) Smag-82 | cells that express FGF receptors | 1c, 2c | Hair growth and development |
| FGF6 Heparin-Binding Growth Factor-6 (HBGF-6) HST-2 | cells that express FGF receptors | 1c, 2c, 4 | Skeletal muscle development |
| FGF7/KGF (Keratinocyte Growth Factor) HST-6 Heparin-Binding Growth Factor-7 (HBGF-7) | keratinocytes and epithelial cells that express FGF receptor 2b | 2b | Keratinocyte growth factor, kidney and lung development, angiogenesis and wound healing |
| FGF8 Androgen-Induced Growth Factor (AIGF)Heparin-Binding Growth Factor-8 (HBGF-8) | mammary carcinoma cells and other cells that express FGF receptors | 2c, 3c, 4 (possibly 1c) | Limb, central nervous system, cardiac outflow tract development |
| FGF9 Glia Activating Factor (GAF)Heparin-Binding Growth Factor-9 (HBGF-9) | glial cells, astrocyte cells and other cells that express FGF receptors | 1c, 2c, 3b, 3c, 4 | Glia-activating factor, motor neuron survival, lung and testes development |
| A Keratinocyte growth factor-2 | epithelial cells that express FGF receptor 2b | 2b | Wound healing, multi-organ including limb and lung development |
| FGF11 FGFB Fibroblast growth Factor Homologous Factor-3(FHF-3) | unknown to date | unknown to date | Appears to be involved in nervous system development and function |
| FGF12 FGFC Fibroblast growth factor Homologous Factor-1(FHF-1) | NIH3T3 fibroblast cell line | 1, 2, 3, 4 | Appears to be involved in nervous system development and function |
| FGF13 FGFD Fibroblast growth Factor Homologous Factor-2(FHF-2) | unknown to date | unknown to date | Appears to be involved in nervous system development and function |
| FGF14 FGFE Fibroblast growth factor Homologous Factor-4(FHF-4) | unknown to date | unknown to date | Regulates central nervous system development and function |
| FGF15 FGFF, identified in mouse not human | cells that express FGF receptor 4 | 4 | Regulator of cell division and patterning in specific regions of embryonic brain, spinal cord and sensory organs |
| FGF16 FGFG | cells that express FGF receptors | 2c, 3c | Central nervous system development |
| FGF17 FGFH | cells that express FGF receptors | 1c, 2c, 3c, 4 | Signals induction and patterning of embryonic brain |
| FGF18 zFGF5 FGFI | cells that express FGF receptors | 1c, 2c, 3c, 4 | An essential regulator of long bone and calvarial development |
| FGF19 FGFJ, identified in human only | cells that express FGF receptor 4 | 4 | Expressed during brain development and during embryogenesis, regulates multiple metabolic processes in adulthood |
| FGF20 FGFK | epithelial and mesenchymal cells | 1c, 2c, 3c | Expressed during limb and brain development |
| FGF21 FGFL | neurons, beta cells | 1c | Expressed in liver, brain, skeletal muscle; may play a role in metabolic disease |
| FGF22 FGFM | hair follicle, skin, keratinocytes, neurons | 2b | May be involved in cutaneous development and repair, and brain development |
| FGF23 FGFN | renal proximal epithelial cells | 3c | Expressed in brain and thymus, regulates phosphate homeostasis, mutant in hypophosphatemic rickets, regulates multiple metabolic processes in adulthood |
References
- Beenken A, Mohammadi M (2009) The FGF family: biology, pathophysiology and therapy. Nat Rev Drug Discov 8(3):235–253.
- Ornitz DM, Itoh N (2001) Fibroblast growth factors. Genome Biol 2(3):REVIEWS3005.
- Sochacka M, Opalinski L, Szymczyk J, et al. (2020) FHF1 is a bona fide fibroblast growth factor that activates cellular signaling in FGFR-dependent manner. Cell Commun Signal 18(1):69.
- Yun YR, Won JE, Jeon E, et al. (2010) Fibroblast growth factors: biology, function, and application for tissue regeneration. J Tissue Eng 2010:218142.
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