Basic fibroblast growth factor
|, BFGF, FGF-2, FGFB, HBGF-2, fibroblast growth factor 2|
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.
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.
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.
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.
- Anxiety disorders
- Fibroblast growth factor
- Growth factor
- Proteases in angiogenesis
- Receptor (biochemistry)
- Signal transduction
- GRCh38: Ensembl release 89: ENSG00000138685 - Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000037225 - Ensembl, May 2017
- "Human PubMed Reference:".
- "Mouse PubMed Reference:".
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.