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Fibroblast growth factor 2

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Growth factor and signaling protein otherwise known as FGF2
FGF2
Available structures
PDBOrtholog 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
AliasesFGF2, BFGF, FGF-2, FGFB, HBGF-2, fibroblast growth factor 2
External IDsOMIM: 134920; MGI: 95516; HomoloGene: 1521; GeneCards: FGF2; OMA:FGF2 - orthologs
Gene location (Human)
Chromosome 4 (human)
Chr.Chromosome 4 (human)
Chromosome 4 (human)Genomic location for FGF2Genomic location for FGF2
Band4q28.1Start122,826,708 bp
End122,898,236 bp
Gene location (Mouse)
Chromosome 3 (mouse)
Chr.Chromosome 3 (mouse)
Chromosome 3 (mouse)Genomic location for FGF2Genomic location for FGF2
Band3 B|3 18.41 cMStart37,402,495 bp
End37,464,257 bp
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • cartilage tissue

  • Epithelium of choroid plexus

  • Achilles tendon

  • smooth muscle tissue

  • stromal cell of endometrium

  • Descending thoracic aorta

  • adipose tissue

  • retinal pigment epithelium

  • subcutaneous adipose tissue

  • muscle layer of sigmoid colon
Top expressed in
  • ascending aorta

  • aortic valve

  • vas deferens

  • efferent ductule

  • ankle

  • decidua

  • gastrula

  • epididymis

  • carotid body

  • esophagus
More reference expression data
BioGPS


More reference expression data
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

2247

14173

Ensembl

ENSG00000138685

ENSMUSG00000037225

UniProt

P09038

P15655

RefSeq (mRNA)

NM_002006
NM_001361665

NM_008006

RefSeq (protein)

NP_001997
NP_001348594

NP_032032

Location (UCSC)Chr 4: 122.83 – 122.9 MbChr 3: 37.4 – 37.46 Mb
PubMed search
Wikidata
View/Edit HumanView/Edit Mouse

Fibroblast growth factor 2 (FGF-2), also known as basic fibroblast growth factor (bFGF) and FGF-β, is a growth factor and signaling protein encoded by the FGF2 gene. 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.

Function

Like other FGF family members, basic fibroblast growth factor possesses 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.

Evidence has shown that low levels of FGF-2 play a key role in the incidence of excessive anxiety.

Additionally, FGF-2 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. FGF-2, 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. The nuclear form of FGF2 functions in mRNA export

FGF-2 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.

Since its first isolation from the bovine pituitary, FGF2 has become a prominent signaling protein studied in bovine reproduction. It has been found in cumulus cells that surround the oocyte and evidence on such early reproductive function indicates FGF2 may promote meiotic resumption and prevent cumulus cell apoptosis. FGF2 is also produced by the uterine epithelium, secreted into the lumen, and acts on the developing embryo and conceptus. Work in mice previously established that FGF2 plays a role in primitive endoderm (PE) development. Research with bovine embryos has since noted this same phenomenon. Extended blastocyst cultures with FGF2-supplemented media observed that FGF2 increases PE outgrowths via proliferation. Knockout models of the FGF receptor and its kinase activity appears to alter the cellular expression of NANOG and GATA4 (transcription factors essential for proper cell differentiation and embryonic development), indicating a specific role of FGF2 in PE specification and subsequent blastocyst development rates. Culture media supplemented with combinations of FGF2, EGF and IGF2 have found similar results and indicate that FGF2 may activate the AKT pathway for trophoblastic cell line growth. Together, this showcases the key roles FGF2 plays in bovine embryo development, as similarly described in other mammalian species.

Interactions

Fibroblast growth factor 2 has been shown to interact with casein kinase 2, alpha 1, RPL6, ribosomal protein S19 and API5.

See also

References

  1. ^ GRCh38: Ensembl release 89: ENSG00000138685Ensembl, May 2017
  2. ^ GRCm38: Ensembl release 89: ENSMUSG00000037225Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 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. doi:10.1002/j.1460-2075.1990.tb07454.x. PMC 551973. PMID 1697263.
  6. 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. S2CID 33214466.
  7. ^ 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. Bibcode:1991NYASA.638..109F. doi:10.1111/j.1749-6632.1991.tb49022.x. PMID 1785797. S2CID 45425517.
  8. 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.
  9. 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. S2CID 2305986.
  10. 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. S2CID 14251918.
  11. 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.
  12. 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/endo.141.12.7851. PMID 11108268.
  13. 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.
  14. 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.
  15. 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. PMC 4558932. PMID 26334535.
  16. ^ Bong SM, Bae SH, Song B, Gwak H, Yang SW, Kim S, Nam S, Rajalingam K, Oh SJ, Kim TW, Park S, Jang H, Lee BI (June 2020). "Regulation of mRNA Export Through API5 and Nuclear FGF2 Interaction". Nucleic Acids Research. 48 (11): 6340–6352. doi:10.1093/nar/gkaa335. PMC 7293033. PMID 32383752.
  17. 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.
  18. Benington L, Rajan G, Locher C, Lim LY (June 2020). "Fibroblast Growth Factor 2-A Review of Stabilisation Approaches for Clinical Applications". Pharmaceutics. 12 (6): 508. doi:10.3390/pharmaceutics12060508. PMC 7356611. PMID 32498439.
  19. Barros RG, Lima PF, Soares AC, Sanches L, Price CA, Buratini J (May 2019). "Fibroblast growth factor 2 regulates cumulus differentiation under the control of the oocyte". Journal of Assisted Reproduction and Genetics. 36 (5): 905–913. doi:10.1007/s10815-019-01436-7. PMC 6541720. PMID 30887159.
  20. ^ Yang QE, Fields SD, Zhang K, Ozawa M, Johnson SE, Ealy AD (November 2011). "Fibroblast growth factor 2 promotes primitive endoderm development in bovine blastocyst outgrowths". Biology of Reproduction. 85 (5): 946–953. doi:10.1095/biolreprod.111.093203. PMID 21778141.
  21. Fields SD, Hansen PJ, Ealy AD (May 2011). "Fibroblast growth factor requirements for in vitro development of bovine embryos". Theriogenology. 75 (8): 1466–1475. doi:10.1016/j.theriogenology.2010.12.007. PMID 21295834.
  22. Xie M, McCoski SR, Johnson SE, Rhoads ML, Ealy AD (February 2017). "Combinatorial effects of epidermal growth factor, fibroblast growth factor 2 and insulin-like growth factor 1 on trophoblast cell proliferation and embryogenesis in cattle". Reproduction, Fertility, and Development. 29 (2): 419–430. doi:10.1071/RD15226. PMID 26304178.
  23. 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.
  24. 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.
  25. 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

PDB gallery
  • 1bas: THREE-DIMENSIONAL STRUCTURES OF ACIDIC AND BASIC FIBROBLAST GROWTH FACTORS 1bas: THREE-DIMENSIONAL STRUCTURES OF ACIDIC AND BASIC FIBROBLAST GROWTH FACTORS
  • 1bfb: BASIC FIBROBLAST GROWTH FACTOR COMPLEXED WITH HEPARIN TETRAMER FRAGMENT 1bfb: BASIC FIBROBLAST GROWTH FACTOR COMPLEXED WITH HEPARIN TETRAMER FRAGMENT
  • 1bfc: BASIC FIBROBLAST GROWTH FACTOR COMPLEXED WITH HEPARIN HEXAMER FRAGMENT 1bfc: BASIC FIBROBLAST GROWTH FACTOR COMPLEXED WITH HEPARIN HEXAMER FRAGMENT
  • 1bff: THE 154 AMINO ACID FORM OF HUMAN BASIC FIBROBLAST GROWTH FACTOR 1bff: THE 154 AMINO ACID FORM OF HUMAN BASIC FIBROBLAST GROWTH FACTOR
  • 1bfg: CRYSTAL STRUCTURE OF BASIC FIBROBLAST GROWTH FACTOR AT 1.6 ANGSTROMS RESOLUTION 1bfg: CRYSTAL STRUCTURE OF BASIC FIBROBLAST GROWTH FACTOR AT 1.6 ANGSTROMS RESOLUTION
  • 1bla: BASIC FIBROBLAST GROWTH FACTOR (FGF-2) MUTANT WITH CYS 78 REPLACED BY SER AND CYS 96 REPLACED BY SER, NMR 1bla: BASIC FIBROBLAST GROWTH FACTOR (FGF-2) MUTANT WITH CYS 78 REPLACED BY SER AND CYS 96 REPLACED BY SER, NMR
  • 1bld: BASIC FIBROBLAST GROWTH FACTOR (FGF-2) MUTANT WITH CYS 78 REPLACED BY SER AND CYS 96 REPLACED BY SER, NMR 1bld: BASIC FIBROBLAST GROWTH FACTOR (FGF-2) MUTANT WITH CYS 78 REPLACED BY SER AND CYS 96 REPLACED BY SER, NMR
  • 1cvs: CRYSTAL STRUCTURE OF A DIMERIC FGF2-FGFR1 COMPLEX 1cvs: CRYSTAL STRUCTURE OF A DIMERIC FGF2-FGFR1 COMPLEX
  • 1ev2: CRYSTAL STRUCTURE OF FGF2 IN COMPLEX WITH THE EXTRACELLULAR LIGAND BINDING DOMAIN OF FGF RECEPTOR 2 (FGFR2) 1ev2: CRYSTAL STRUCTURE OF FGF2 IN COMPLEX WITH THE EXTRACELLULAR LIGAND BINDING DOMAIN OF FGF RECEPTOR 2 (FGFR2)
  • 1fga: REFINEMENT OF THE STRUCTURE OF HUMAN BASIC FIBROBLAST GROWTH FACTOR AT 1.6 ANGSTROMS RESOLUTION AND ANALYSIS OF PRESUMED HEPARIN BINDING SITES BY SELENATE SUBSTITUTION 1fga: REFINEMENT OF THE STRUCTURE OF HUMAN BASIC FIBROBLAST GROWTH FACTOR AT 1.6 ANGSTROMS RESOLUTION AND ANALYSIS OF PRESUMED HEPARIN BINDING SITES BY SELENATE SUBSTITUTION
  • 1fq9: CRYSTAL STRUCTURE OF A TERNARY FGF2-FGFR1-HEPARIN COMPLEX 1fq9: CRYSTAL STRUCTURE OF A TERNARY FGF2-FGFR1-HEPARIN COMPLEX
  • 1ii4: CRYSTAL STRUCTURE OF SER252TRP APERT MUTANT FGF RECEPTOR 2 (FGFR2) IN COMPLEX WITH FGF2 1ii4: CRYSTAL STRUCTURE OF SER252TRP APERT MUTANT FGF RECEPTOR 2 (FGFR2) IN COMPLEX WITH FGF2
  • 1iil: CRYSTAL STRUCTURE OF PRO253ARG APERT MUTANT FGF RECEPTOR 2 (FGFR2) IN COMPLEX WITH FGF2 1iil: CRYSTAL STRUCTURE OF PRO253ARG APERT MUTANT FGF RECEPTOR 2 (FGFR2) IN COMPLEX WITH FGF2
  • 2bfh: CRYSTAL STRUCTURE OF BASIC FIBROBLAST GROWTH FACTOR AT 1.6 ANGSTROMS RESOLUTION 2bfh: CRYSTAL STRUCTURE OF BASIC FIBROBLAST GROWTH FACTOR AT 1.6 ANGSTROMS RESOLUTION
  • 2fgf: THREE-DIMENSIONAL STRUCTURE OF HUMAN BASIC FIBROBLAST GROWTH FACTOR, A STRUCTURAL HOMOLOG OF INTERLEUKIN 1BETA 2fgf: THREE-DIMENSIONAL STRUCTURE OF HUMAN BASIC FIBROBLAST GROWTH FACTOR, A STRUCTURAL HOMOLOG OF INTERLEUKIN 1BETA
  • 4fgf: REFINEMENT OF THE STRUCTURE OF HUMAN BASIC FIBROBLAST GROWTH FACTOR AT 1.6 ANGSTROMS RESOLUTION AND ANALYSIS OF PRESUMED HEPARIN BINDING SITES BY SELENATE SUBSTITUTION 4fgf: REFINEMENT OF THE STRUCTURE OF HUMAN BASIC FIBROBLAST GROWTH FACTOR AT 1.6 ANGSTROMS RESOLUTION AND ANALYSIS OF PRESUMED HEPARIN BINDING SITES BY SELENATE SUBSTITUTION

External links

Growth factors
Fibroblast
FGF receptor ligands:
KGF
FGF homologous factors:
hormone-like: FGF15/19
EGF-like domain
TGFβ pathway
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