Biology:Basic fibroblast growth factor

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Short description: Growth factor and signaling protein otherwise known as FGF2


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Fibroblast growth factor 2, 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 binds to and exerts effects via specific fibroblast growth factor receptor (FGFR) proteins, themselves a family of closely related molecules. Fibroblast growth factor protein was first purified in 1975; soon thereafter three variants were isolated: 'basic FGF' (FGF2); Heparin-binding growth factor-2; and Endothelial cell growth factor-2. Gene sequencing revealed that this group is the same FGF2 protein and is a member of a family of FGF proteins.[3][4]

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.[5]

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.[6]

Recent evidence has shown that low levels of FGF2 play a key role in the incidence of excessive anxiety.[7]

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.[8] It is necessary in mouse-feeder cell dependent culture systems, as well as in feeder and serum-free culture systems.[9] 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.[10] However, a low concentration of bFGF (10 ng/mL) may exert an inhibitory effect on osteoblast differentiation.[11] The nuclear form of FGF2 functions in mRNA export[12]

FGF2 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.[13]

Interactions

Basic fibroblast growth factor has been shown to interact with casein kinase 2, alpha 1,[14] RPL6,[15] ribosomal protein S19[16] and API5.[12]

See also

References

  1. "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. September 1990. doi:10.1002/j.1460-2075.1990.tb07454.x. PMID 1697263. 
  2. "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. 1998. doi:10.1159/000015129. PMID 9925931. 
  3. 3.0 3.1 "Basic fibroblast growth factor gene expression". Annals of the New York Academy of Sciences 638 (1): 109–26. December 1991. doi:10.1111/j.1749-6632.1991.tb49022.x. PMID 1785797. Bibcode1991NYASA.638..109F. 
  4. "The heparin-binding (fibroblast) growth factor family of proteins". Annual Review of Biochemistry 58: 575–606. 1989. doi:10.1146/annurev.bi.58.070189.003043. PMID 2549857. 
  5. "Adipocyte-secreted factors increase osteoblast proliferation and the OPG/RANKL ratio to influence osteoclast formation". Molecular and Cellular Endocrinology 349 (2): 180–8. February 2012. doi:10.1016/j.mce.2011.10.018. PMID 22040599. 
  6. "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. December 2003. doi:10.1161/01.CIR.0000105723.91637.1C. PMID 14656920. 
  7. "A new role for FGF2 as an endogenous inhibitor of anxiety". The Journal of Neuroscience 29 (19): 6379–87. May 2009. doi:10.1523/JNEUROSCI.4829-08.2009. PMID 19439615. 
  8. "Bone morphogenetic proteins induce gremlin, a protein that limits their activity in osteoblasts". Endocrinology 141 (12): 4558–63. December 2000. doi:10.1210/endo.141.12.7851. PMID 11108268. http://endo.endojournals.org/cgi/pmidlookup?view=long&pmid=11108268. 
  9. "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. July 2006. doi:10.1016/j.bbrc.2006.05.086. PMID 16753134. 
  10. "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. January 2013. doi:10.1016/j.bbrc.2012.11.067. PMID 23206696. 
  11. "Epidermal growth factor enhances osteogenic differentiation of dental pulp stem cells in vitro". Head & Face Medicine 11: 29. September 2015. doi:10.1186/s13005-015-0086-5. PMID 26334535. 
  12. 12.0 12.1 "Regulation of mRNA Export Through API5 and Nuclear FGF2 Interaction". Nucleic Acids Research 48 (11): 6340–6352. June 2020. doi:10.1093/nar/gkaa335. PMID 32383752. 
  13. "The ins and outs of fibroblast growth factor receptor signalling". Clinical Science 127 (4): 217–31. August 2014. doi:10.1042/CS20140100. PMID 24780002. http://www.clinsci.org/content/127/4/217. 
  14. "Binding of FGF-1 variants to protein kinase CK2 correlates with mitogenicity". The EMBO Journal 21 (15): 4058–69. August 2002. doi:10.1093/emboj/cdf402. PMID 12145206. 
  15. "Intracellular association of FGF-2 with the ribosomal protein L6/TAXREB107". Biochemical and Biophysical Research Communications 252 (2): 524–8. November 1998. doi:10.1006/bbrc.1998.9677. PMID 9826564. 
  16. "Fibroblast growth factor-2 interacts with free ribosomal protein S19". Biochemical and Biophysical Research Communications 289 (2): 591–6. November 2001. doi:10.1006/bbrc.2001.5960. PMID 11716516. 

Further reading

External links


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