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. 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. 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.

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. 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.

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.

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

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. It is necessary in mouse-feeder cell dependent culture systems, as well as in feeder and serum-free culture systems. 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. However, a low concentration of bFGF (10 ng/mL) may exert an inhibitory effect on osteoblast differentiation.

Interactions

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

See also

• Angiogenesis
• Anxiety disorders
• Cytokine
• Fibroblast growth factor
• Growth factor
• Proteases in angiogenesis
• Receptor (biochemistry)
• Signal transduction

Further reading

• Ornitz DM, Itoh N (2001). "Fibroblast growth factors". Genome Biology. 2 (3): REVIEWS3005. doi:10.1186/gb-2001-2-3-reviews3005. PMC 138918. PMID 11276432.
• Orpana A, Salven P (February 2002). "Angiogenic and lymphangiogenic molecules in hematological malignancies". Leukemia & Lymphoma. 43 (2): 219–24. doi:10.1080/10428190290005964. PMID 11999550.
• Marie PJ, Debiais F, Haÿ E (2003). "Regulation of human cranial osteoblast phenotype by FGF-2, FGFR-2 and BMP-2 signaling". Histology and Histopathology. 17 (3): 877–85. doi:10.14670/HH-17.877. PMID 12168799.
• Zhao XC, Zhang LM, Tong DY, An P, Jiang C, Zhao P, Chen WM, Wang J (March 2013). "Propofol increases expression of basic fibroblast growth factor after transient cerebral ischemia in rats". Neurochemical Research. 38 (3): 530–7. doi:10.1007/s11064-012-0945-4. PMC 3574197. PMID 23247820.
• Vincent T, Saklatvala J (June 2006). "Basic fibroblast growth factor: an extracellular mechanotransducer in articular cartilage?". Biochemical Society Transactions. 34 (Pt 3): 456–7. doi:10.1042/BST0340456. PMID 16709186.
• Ribatti D, Vacca A, Rusnati M, Presta M (2007). "The discovery of basic fibroblast growth factor/fibroblast growth factor-2 and its role in haematological malignancies". Cytokine & Growth Factor Reviews. 18 (3–4): 327–34. doi:10.1016/j.cytogfr.2007.04.011. PMID 17537668.
• Watson R, Anthony F, Pickett M, Lambden P, Masson GM, Thomas EJ (September 1992). "Reverse transcription with nested polymerase chain reaction shows expression of basic fibroblast growth factor transcripts in human granulosa and cumulus cells from in vitro fertilisation patients". Biochemical and Biophysical Research Communications. 187 (3): 1227–31. doi:10.1016/0006-291X(92)90434-M. PMID 1417798.
• Zhu X, Komiya H, Chirino A, Faham S, Fox GM, Arakawa T, Hsu BT, Rees DC (January 1991). "Three-dimensional structures of acidic and basic fibroblast growth factors". Science. 251 (4989): 90–3. doi:10.1126/science.1702556. PMID 1702556.
• Eriksson AE, Cousens LS, Weaver LH, Matthews BW (April 1991). "Three-dimensional structure of human basic fibroblast growth factor". Proceedings of the National Academy of Sciences of the United States of America. 88 (8): 3441–5. doi:10.1073/pnas.88.8.3441. PMC 51463. PMID 1707542.
• Ago H, Kitagawa Y, Fujishima A, Matsuura Y, Katsube Y (September 1991). "Crystal structure of basic fibroblast growth factor at 1.6 A resolution". Journal of Biochemistry. 110 (3): 360–3. PMID 1769963.
• Zhang JD, Cousens LS, Barr PJ, Sprang SR (April 1991). "Three-dimensional structure of human basic fibroblast growth factor, a structural homolog of interleukin 1 beta". Proceedings of the National Academy of Sciences of the United States of America. 88 (8): 3446–50. doi:10.1073/pnas.88.8.3446. PMC 51464. PMID 1849658.
• Wu DQ, Kan MK, Sato GH, Okamoto T, Sato JD (September 1991). "Characterization and molecular cloning of a putative binding protein for heparin-binding growth factors". The Journal of Biological Chemistry. 266 (25): 16778–85. PMID 1885605.
• Fukushima Y, Byers MG, Fiddes JC, Shows TB (1991). "The human basic fibroblast growth factor gene (FGFB) is assigned to chromosome 4q25". Cytogenetics and Cell Genetics. 54 (3–4): 159–60. doi:10.1159/000132983. PMID 2265560.
• Lafage-Pochitaloff M, Galland F, Simonetti J, Prats H, Mattei MG, Birnbaum D (1990). "The human basic fibroblast growth factor gene is located on the long arm of chromosome 4 at bands q26-q27". Oncogene Research. 5 (3): 241–4. PMID 2320377.
• Story MT, Esch F, Shimasaki S, Sasse J, Jacobs SC, Lawson RK (February 1987). "Amino-terminal sequence of a large form of basic fibroblast growth factor isolated from human benign prostatic hyperplastic tissue". Biochemical and Biophysical Research Communications. 142 (3): 702–9. doi:10.1016/0006-291X(87)91471-9. PMID 2435284.
• Kurokawa T, Sasada R, Iwane M, Igarashi K (March 1987). "Cloning and expression of cDNA encoding human basic fibroblast growth factor". FEBS Letters. 213 (1): 189–94. doi:10.1016/0014-5793(87)81489-8. PMID 2435575.
• Prats H, Kaghad M, Prats AC, Klagsbrun M, Lélias JM, Liauzun P, Chalon P, Tauber JP, Amalric F, Smith JA (March 1989). "High molecular mass forms of basic fibroblast growth factor are initiated by alternative CUG codons". Proceedings of the National Academy of Sciences of the United States of America. 86 (6): 1836–40. doi:10.1073/pnas.86.6.1836. PMC 286799. PMID 2538817.
• Florkiewicz RZ, Sommer A (June 1989). "Human basic fibroblast growth factor gene encodes four polypeptides: three initiate translation from non-AUG codons". Proceedings of the National Academy of Sciences of the United States of America. 86 (11): 3978–81. doi:10.1073/pnas.86.11.3978. PMC 287371. PMID 2726761.
• Abraham JA, Whang JL, Tumolo A, Mergia A, Fiddes JC (1987). "Human basic fibroblast growth factor: nucleotide sequence, genomic organization, and expression in mammalian cells". Cold Spring Harbor Symposia on Quantitative Biology. 51 Pt 1: 657–68. doi:10.1101/sqb.1986.051.01.078. PMID 3472745.
• Sommer A, Brewer MT, Thompson RC, Moscatelli D, Presta M, Rifkin DB (April 1987). "A form of human basic fibroblast growth factor with an extended amino terminus". Biochemical and Biophysical Research Communications. 144 (2): 543–50. doi:10.1016/S0006-291X(87)80001-3. PMID 3579930.

External links

• Basic+Fibroblast+Growth+Factor at the US National Library of Medicine Medical Subject Headings (MeSH)
• Human FGF2 genome location and FGF2 gene details page in the UCSC Genome Browser.