Basic fibroblast growth factor

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FGF2, also known as basic fibroblast growth factor (bFGF) and FGF-β, is a growth factor and signaling protein encoded by the FGF2 gene.[1][2] It is synthesized primarily as a 155 amino acid polypeptide, resulting in an 18 kDa protein. However, there are four alternate start codons which provide N-terminal extensions of 41, 46, 55, or 133 amino acids, resulting in proteins of 22 kDa (196 aa total), 22.5 kDa (201 aa total), 24 kDa (210 aa total) and 34 kDa (288 aa total), respectively.[3] Generally, the 155 aa/18 kDa low molecular weight (LMW) form is considered cytoplasmic and can be secreted from the cell, whereas the high molecular weight (HMW) forms are directed to the cell's nucleus.[4]

Fibroblast growth factor protein was first purified in 1975, but soon afterwards others using different conditions isolated basic FGF, Heparin-binding growth factor-2, and Endothelial cell growth factor-2. Gene sequencing revealed that this group was in fact the same FGF2 protein and that it was a member of a family of FGF proteins.[3][5] FGF2 binds to and exerts effects via specific fibroblast growth factor receptor (FGFR) proteins which themselves constitute a family of closely related molecules.

Function

Like other FGF family members, basic fibroblast growth factor possess broad mitogenic and cell survival activities, and is involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion.

In normal tissue, bFGF is present in basement membranes and in the subendothelial extracellular matrix of blood vessels. It stays membrane-bound as long as there is no signal peptide.

It has been hypothesized that, during both wound healing of normal tissues and tumor development, the action of heparan sulfate-degrading enzymes activates bFGF, thus mediating the formation of new blood vessels, a process known as angiogenesis.

In addition, it is synthesized and secreted by human adipocytes and the concentration of FGF2 correlates with the BMI in blood samples. It was also shown to act on preosteoblasts – in the form of an increased proliferation – after binding to fibroblast growth factor receptor 1 and activating phosphoinositide 3-kinase.[6]

FGF2 has been shown in preliminary animal studies to protect the heart from injury associated with a heart attack, reducing tissue death and promoting improved function after reperfusion.[7]

Recent evidence has shown that low levels of FGF2 play a key role in the incidence of excessive anxiety.[8]

Additionally, FGF2 is a critical component of human embryonic stem cell culture medium; the growth factor is necessary for the cells to remain in an undifferentiated state, although the mechanisms by which it does this are poorly defined. It has been demonstrated to induce gremlin expression which in turn is known to inhibit the induction of differentiation by bone morphogenetic proteins.[9] It is necessary in mouse-feeder cell dependent culture systems, as well as in feeder and serum-free culture systems.[10] FGF2, in conjunction with BMP4, promote differentiation of stem cells to mesodermal lineages. After differentiation, BMP4 and FGF2 treated cells generally produce higher amounts of osteogenic and chondrogenic differentiation than untreated stem cells.[11] However, a low concentration of bFGF (10 ng/mL) may exert an inhibitory effect on osteoblast differentiation.[12]

Interactions

Basic fibroblast growth factor has been shown to interact with casein kinase 2, alpha 1,[13] RPL6[14] and ribosomal protein S19.[15]

See also

References

  1. Dionne CA, Crumley G, Bellot F, Kaplow JM, Searfoss G, Ruta M, Burgess WH, Jaye M, Schlessinger J (September 1990). "Cloning and expression of two distinct high-affinity receptors cross-reacting with acidic and basic fibroblast growth factors". The EMBO Journal. 9 (9): 2685–92. PMC 551973. PMID 1697263.
  2. Kim HS (1998). "Assignment1 of the human basic fibroblast growth factor gene FGF2 to chromosome 4 band q26 by radiation hybrid mapping". Cytogenetics and Cell Genetics. 83 (1–2): 73. doi:10.1159/000015129. PMID 9925931.
  3. 3.0 3.1 Florkiewicz RZ, Shibata F, Barankiewicz T, Baird A, Gonzalez AM, Florkiewicz E, Shah N (December 1991). "Basic fibroblast growth factor gene expression". Annals of the New York Academy of Sciences. 638 (1): 109–26. doi:10.1111/j.1749-6632.1991.tb49022.x. PMID 1785797.
  4. Coleman SJ, Bruce C, Chioni AM, Kocher HM, Grose RP (August 2014). "The ins and outs of fibroblast growth factor receptor signalling". Clinical Science. 127 (4): 217–31. doi:10.1042/CS20140100. PMID 24780002.
  5. Burgess WH, Maciag T (1989). "The heparin-binding (fibroblast) growth factor family of proteins". Annual Review of Biochemistry. 58: 575–606. doi:10.1146/annurev.bi.58.070189.003043. PMID 2549857.
  6. Kühn MC, Willenberg HS, Schott M, Papewalis C, Stumpf U, Flohé S, Scherbaum WA, Schinner S (February 2012). "Adipocyte-secreted factors increase osteoblast proliferation and the OPG/RANKL ratio to influence osteoclast formation". Molecular and Cellular Endocrinology. 349 (2): 180–8. doi:10.1016/j.mce.2011.10.018. PMID 22040599.
  7. House SL, Bolte C, Zhou M, Doetschman T, Klevitsky R, Newman G, Schultz Jel J (December 2003). "Cardiac-specific overexpression of fibroblast growth factor-2 protects against myocardial dysfunction and infarction in a murine model of low-flow ischemia". Circulation. 108 (25): 3140–8. doi:10.1161/01.CIR.0000105723.91637.1C. PMID 14656920.
  8. Perez JA, Clinton SM, Turner CA, Watson SJ, Akil H (May 2009). "A new role for FGF2 as an endogenous inhibitor of anxiety". The Journal of Neuroscience. 29 (19): 6379–87. doi:10.1523/JNEUROSCI.4829-08.2009. PMC 2748795. PMID 19439615.
  9. Pereira RC, Economides AN, Canalis E (December 2000). "Bone morphogenetic proteins induce gremlin, a protein that limits their activity in osteoblasts". Endocrinology. 141 (12): 4558–63. doi:10.1210/en.141.12.4558. PMID 11108268.
  10. Liu Y, Song Z, Zhao Y, Qin H, Cai J, Zhang H, Yu T, Jiang S, Wang G, Ding M, Deng H (July 2006). "A novel chemical-defined medium with bFGF and N2B27 supplements supports undifferentiated growth in human embryonic stem cells". Biochemical and Biophysical Research Communications. 346 (1): 131–9. doi:10.1016/j.bbrc.2006.05.086. PMID 16753134.
  11. Lee TJ, Jang J, Kang S, Jin M, Shin H, Kim DW, Kim BS (January 2013). "Enhancement of osteogenic and chondrogenic differentiation of human embryonic stem cells by mesodermal lineage induction with BMP-4 and FGF2 treatment". Biochemical and Biophysical Research Communications. 430 (2): 793–7. doi:10.1016/j.bbrc.2012.11.067. PMID 23206696.
  12. Del Angel-Mosqueda C, Gutiérrez-Puente Y, López-Lozano AP, Romero-Zavaleta RE, Mendiola-Jiménez A, Medina-De la Garza CE, Márquez-M M, De la Garza-Ramos MA (September 2015). "Epidermal growth factor enhances osteogenic differentiation of dental pulp stem cells in vitro". Head & Face Medicine. 11: 29. doi:10.1186/s13005-015-0086-5. PMID 26334535.
  13. Skjerpen CS, Nilsen T, Wesche J, Olsnes S (August 2002). "Binding of FGF-1 variants to protein kinase CK2 correlates with mitogenicity". The EMBO Journal. 21 (15): 4058–69. doi:10.1093/emboj/cdf402. PMC 126148. PMID 12145206.
  14. Shen B, Arese M, Gualandris A, Rifkin DB (November 1998). "Intracellular association of FGF-2 with the ribosomal protein L6/TAXREB107". Biochemical and Biophysical Research Communications. 252 (2): 524–8. doi:10.1006/bbrc.1998.9677. PMID 9826564.
  15. Soulet F, Al Saati T, Roga S, Amalric F, Bouche G (November 2001). "Fibroblast growth factor-2 interacts with free ribosomal protein S19". Biochemical and Biophysical Research Communications. 289 (2): 591–6. doi:10.1006/bbrc.2001.5960. PMID 11716516.

Further reading

External links

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