Basic fibroblast growth factor

Source: Wikipedia, the free encyclopedia.
FGF2
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
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[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Fibroblast growth factor 2, also known as basic fibroblast growth factor (bFGF) and FGF-β, is a

signaling protein encoded by the FGF2 gene.[5][6] 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.[7][8]

Function

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

tissue repair
, tumor growth and invasion.

In normal tissue, bFGF is present in

membrane-bound as long as there is no signal peptide
.

It has been hypothesized that, during both

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

preosteoblasts – in the form of an increased proliferation – after binding to fibroblast growth factor receptor 1 and activating phosphoinositide 3-kinase.[9]

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.[10]

Recent evidence has shown that low levels of FGF2 play a key role in the incidence of excessive anxiety.[11]

Additionally, FGF2 is a critical component of human

bone morphogenetic proteins.[12] It is necessary in mouse-feeder cell dependent culture systems, as well as in feeder and serum-free culture systems.[13] 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.[14] However, a low concentration of bFGF (10 ng/mL) may exert an inhibitory effect on osteoblast differentiation.[15] The nuclear form of FGF2 functions in mRNA export[16]

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.[7] 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.[17]

Since its first isolation from the bovine pituitary,[18] 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.[19] 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.[20] 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.[20][21] 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.[22] Together, this showcases the key roles FGF2 plays in bovine embryo development, as similarly described in other mammalian species.

Interactions

Basic fibroblast growth factor has been shown to

ribosomal protein S19[25] and API5.[16]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000138685 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000037225 – Ensembl, 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. PMID 1697263
    .
  6. S2CID 33214466
    .
  7. ^
    S2CID 45425517
    .
  8. PMID 2549857
    .
  9. S2CID 2305986
    .
  10. S2CID 14251918
    .
  11. PMID 19439615
    .
  12. PMID 11108268
    .
  13. PMID 16753134
    .
  14. PMID 23206696
    .
  15. PMID 26334535
    .
  16. ^
    PMID 32383752
    .
  17. PMID 24780002
    .
  18. PMID 32498439
    .
  19. PMID 30887159
    .
  20. ^
    PMID 21778141
    .
  21. PMID 21295834
    .
  22. PMID 26304178
    .
  23. PMID 12145206
    .
  24. PMID 9826564
    .
  25. PMID 11716516
    .

Further reading

External links
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