Fibroblast growth factor

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Fibroblast growth factors, or FGFs, are a family of growth factors involved in wound healing and embryonic development. The FGFs are heparin-binding proteins and interactions with cell-surface associated heparan sulfate proteoglycans have been shown to be essential for FGF signal transduction.

1 Families
2 Receptors
3 History
4 Function
5 See also
6 References
7 External links

[edit] Families

In humans, 22 members of the FGF family have been identified all of which are structurally related signaling molecules:^[1]

Members FGF1 through FGF10 all bind FGFRs. FGF1 is also known as "Acidic", and FGF2 is also known as basic fibroblast growth factor.
Members FGF11, FGF12, FGF13, and FGF14, also known as FGF homologous factors 1-4 (FHF1-FHF4), have been shown to have distinct functional differences compared to the FGFs. Although these factors possess remarkably similar sequence homology, they do not bind FGFRs and are involved in intracellular processes unrelated to the FGFs.^[2]
Members FGF16 through FGF23 are newer and not as well characterized. There is no #15.

[edit] Receptors

FGF molecules bind to a family of fibroblast growth factor receptor molecules consisting of 4 members (FGFR1, FGFR2, FGFR3, and FGFR4).

Alternate mRNA splicing gives rise to two distinct forms (b and c) of FGFRs1-3 which differ significantly in their ligand-binding profiles.

The signaling complex at the cell surface is believed to be a ternary complex formed between two identical FGF ligands, two identical FGFR subunits and either one or two heparan sulfate chains.

[edit] History

Fibroblast growth factor was found in a cow brain extract by Gospodarowicz and colleagues and tested in a bioassay which caused fibroblasts to proliferate (first published report in 1974).^[3]

They then further fractionated the extract using acidic and basic pH and isolated two slightly different forms that were named "acidic fibroblast growth factor" (FGF1) and "basic fibroblast growth factor" (FGF2). These proteins had a high degree of amino acid identity but were determined to be distinct mitogens.

Not long after FGF1 and FGF2 were isolated, another group isolated a pair of heparin-binding growth factors which they named HBGF-1 and HBGF-2, whilst a third group isolated a pair of growth factors that caused proliferation of cells in a bioassay containing blood vessel endothelium cells which they called ECGF-1 and ECGF-2. These proteins were found to be identical to the acidic and basic FGFs described by Gospodarowicz and coworkers.

[edit] Function

One of the most important functions of bFGF (FGF2) is the promotion of endothelial cell proliferation and the physical organization of endothelial cells into tube-like structures. It thus promotes angiogenesis, the growth of new blood vessels from the pre-existing vasculature. bFGF is a more potent angiogenic factor than VEGF (vascular endothelial growth factor) or PDGF (platelet-derived growth factor). As well as stimulating blood vessel growth, bFGF is an important player in wound healing. It stimulates the proliferation of fibroblasts that give rise to granulation tissue, which fills up a wound space/cavity early in the wound healing process.

It has also been demonstrated that fibroblast growth factors are associated with many developmental processes including mesoderm induction, antero-posterior patterning, neural induction, angiogenesis, axon extension and limb formation.^[4]

They are crucial for the normal development of both vertebrates and invertebrates and any irregularities in their function leads to a range of developmental defects.^[5]^[6]^[7]^[8]

[edit] See also

granulocyte-colony stimulating factor (G-CSF)
granulocyte-macrophage colony stimulating factor (GM-CSF)
nerve growth factor (NGF)
neurotrophins
erythropoietin (EPO)
thrombopoietin (TPO)
myostatin (GDF-8)
Growth Differentiation factor-9 (GDF9)

[edit] References

^ Finklestein SP and Plomaritoglou A. Growth Factors. Chapter 7 In: Head Trauma: Basic, Preclinical, and Clinical Directions. Miller LP and Hayes RL, eds. Co-edited by Newcomb JK. 2001, John Wiley and Sons, Inc. New York. pp. 165 - 187.
^ Olsen, S. K., Garbi, M., Zampieri, N., Eliseenkova, A. V., Ornitz, D. M., Goldfarb, M. and Mohammadi, M. (2003). J Biol Chem 278, 34226-36.
^ Gospodarowicz D (1974). "Localisation of a fibroblast growth factor and its effect alone and with hydrocortisone on 3T3 cell growth". Nature 249 (453): 123-7. PMID 4364816.
^ Bottcher, R. T. and Niehrs, C. (2005). Endocr Rev 26, 63-77.
^ Amaya, E., Musci, T. J. and Kirschner, M. W. (1991). Cell 66, 257-70
^ Borland, C. Z., Schutzman, J. L. and Stern, M. J. (2001). Bioessays 23, 1120-30.
^ Coumoul, X. and Deng, C. X. (2003). Birth Defects Res C Embryo Today 69, 286-304.
^ Sutherland, D., Samakovlis, C. and Krasnow, M. (1996). Cell 87, 1091-1101.