Basic fibroblast growth factor

Fibroblast growth factor 2 (basic)
PDB rendering based on 1bas.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1BAS​, 1BFB​, 1BFC​, 1BFF​, 1BFG​, 1BLA​, 1BLD​, 1CVS​, 1EV2​, 1FGA​, 1FQ9​, 1II4​, 1IIL​, 2BFH​, 2FGF​, 2M49​, 4FGF​, 4OEE​, 4OEF​, 4OEG​
Identifiers
Symbols	FGF2 ; BFGF; FGF-2; FGFB; HBGF-2
External IDs	OMIM: 134920 MGI: 95516 HomoloGene: 1521 ChEMBL: 3107 GeneCards: FGF2 Gene
Gene ontology Molecular function • fibroblast growth factor receptor binding • cytokine activity • protein binding • growth factor activity • heparin binding • ligand-dependent nuclear receptor transcription coactivator activity • chemoattractant activity Cellular component • extracellular region • extracellular space • nucleus Biological process • activation of MAPK activity • branching involved in ureteric bud morphogenesis • positive regulation of endothelial cell proliferation • cell migration involved in sprouting angiogenesis • phosphatidylinositol biosynthetic process • chemotaxis • signal transduction • epidermal growth factor receptor signaling pathway • Ras protein signal transduction • nervous system development • positive regulation of cell proliferation • insulin receptor signaling pathway • fibroblast growth factor receptor signaling pathway • organ morphogenesis • negative regulation of fibroblast migration • positive regulation of phospholipase C activity • growth factor dependent regulation of skeletal muscle satellite cell proliferation • extracellular matrix organization • hyaluronan catabolic process • inositol phosphate biosynthetic process • somatic stem cell maintenance • Fc-epsilon receptor signaling pathway • wound healing • positive regulation of cell fate specification • positive regulation of MAP kinase activity • positive regulation of blood vessel endothelial cell migration • negative regulation of blood vessel endothelial cell migration • positive regulation of phosphatidylinositol 3-kinase activity • innate immune response • regulation of angiogenesis • positive regulation of angiogenesis • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • neurotrophin TRK receptor signaling pathway • phosphatidylinositol-mediated signaling • embryonic morphogenesis • positive chemotaxis • release of sequestered calcium ion into cytosol • positive regulation of cell division • positive regulation of cardiac muscle cell proliferation • negative regulation of cell death • chondroblast differentiation • negative regulation of wound healing • positive regulation of ERK1 and ERK2 cascade • positive regulation of sprouting angiogenesis • regulation of endothelial cell chemotaxis to fibroblast growth factor • positive regulation of endothelial cell chemotaxis to fibroblast growth factor Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2247	14173
Ensembl	ENSG00000138685	ENSMUSG00000037225
UniProt	P09038	P15655
RefSeq (mRNA)	NM_002006	NM_008006
RefSeq (protein)	NP_001997	NP_032032
Location (UCSC)	Chr 4: 122.83 – 122.9 Mb	Chr 3: 37.35 – 37.41 Mb
PubMed search

Basic fibroblast growth factor, also known as bFGF, FGF2 or FGF-β, is a member of the fibroblast growth factor family.^[1]

Function

In normal tissue, basic fibroblast growth factor 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 bFGF correlates with the BMI in blood samples. In this study, bFGF 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.^[2]

bFGF 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.^[3]

Recent evidence has shown that low levels of FGF2 play a key role in the incidence of excessive anxiety.^[4]

Additionally, bFGF 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.^[5] It is necessary in mouse-feeder cell dependent culture systems, as well as in feeder and serum-free culture systems.^[6] FGF2, in conjunction with BMP4, promote differentiation of stem cells to mesodermal lineages. After differentiation, BMP4 and FGF2 treated cells generally produces higher amounts of osteogenic and chondrogenic differentiation than untreated stem cells.^[7]

Interactions

Basic fibroblast growth factor has been shown to interact with casein kinase 2, alpha 1,^[8] RPL6^[9] and ribosomal protein S19.^[10]

See also

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

References

1. 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.
2. Kühn MC, Willenberg HS, Schott M, Papewalis C, Stumpf U, Flohé S, Scherbaum WA, Schinner S (Feb 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.
3. House SL, Bolte C, Zhou M, Doetschman T, Klevitsky R, Newman G, Schultz Jel J (Dec 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.
4. Perez JA, Clinton SM, Turner CA, Watson SJ, Akil H (2009). "A new role for FGF2 as an endogenous inhibitor of anxiety". J. Neurosci. 29 (19): 6379–87. doi:10.1523/JNEUROSCI.4829-08.2009. PMC 2748795. PMID 19439615.
5. Pereira RC, Economides AN, Canalis E (Dec 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.
6. Liu Y, Song Z, Zhao Y, Qin H, Cai J, Zhang H, Yu T, Jiang S, Wang G, Ding M, Deng H (Jul 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.
7. Lee TJ, Jang J, Kang S, Jin M, Shin H, Kim DW, Kim BS (Jan 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.
8. Skjerpen CS, Nilsen T, Wesche J, Olsnes S (Aug 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.
9. Shen B, Arese M, Gualandris A, Rifkin DB (Nov 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.
10. Soulet F, Al Saati T, Roga S, Amalric F, Bouche G (Nov 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

• 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 (Feb 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. PMID 12168799.
• Zhao XC, Zhang LM, Tong DY, An P, Jiang C, Zhao P, Chen WM, Wang J (Mar 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 (Jun 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 (Sep 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 (Jan 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 (Apr 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 (Sep 1991). "Crystal structure of basic fibroblast growth factor at 1.6 A resolution". Journal of Biochemistry 110 (3): 360–3. PMID 1769963.
• Florkiewicz RZ, Shibata F, Barankiewicz T, Baird A, Gonzalez AM, Florkiewicz E, Shah N (1992). "Basic fibroblast growth factor gene expression". Annals of the New York Academy of Sciences 638: 109–26. doi:10.1111/j.1749-6632.1991.tb49022.x. PMID 1785797.
• Zhang JD, Cousens LS, Barr PJ, Sprang SR (Apr 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 (Sep 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 (Feb 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 (Mar 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 (Mar 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 (Jun 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 (Apr 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)