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FGF2

Official Full Name
fibroblast growth factor 2
Organism
Homo sapiens
GeneID
2247
Background
The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members bind heparin and possess broad mitogenic and angiogenic activities. This protein has been implicated in diverse biological processes, such as limb and nervous system development, wound healing, and tumor growth. The mRNA for this gene contains multiple polyadenylation sites, and is alternatively translated from non-AUG (CUG) and AUG initiation codons, resulting in five different isoforms with distinct properties. The CUG-initiated isoforms are localized in the nucleus and are responsible for the intracrine effect, whereas, the AUG-initiated form is mostly cytosolic and is responsible for the paracrine and autocrine effects of this FGF. [provided by RefSeq, Jul 2008]
Synonyms
BFGF; FGFB; FGF-2; HBGF-2;
Bio Chemical Class
Growth factor
Protein Sequence
MVGVGGGDVEDVTPRPGGCQISGRGARGCNGIPGAAAWEAALPRRRPRRHPSVNPRSRAAGSPRTRGRRTEERPSGSRLGDRGRGRALPGGRLGGRGRGRAPERVGGRGRGRGTAAPRAAPAARGSRPGPAGTMAAGSITTLPALPEDGGSGAFPPGHFKDPKRLYCKNGGFFLRIHPDGRVDGVREKSDPHIKLQLQAEERGVVSIKGVCANRYLAMKEDGRLLASKCVTDECFFFERLESNNYNTYRSRKYTSWYVALKRTGQYKLGSKTGPGQKAILFLPMSAKS
Open
Disease
Acne vulgaris, Arterial occlusive disease, Bladder cancer, Multiple myeloma, Neurodegenerative disorder, Retinopathy, Solid tumour/cancer, Stomach cancer
Approved Drug
1 +
Clinical Trial Drug
4 +
Discontinued Drug
2 +

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Detailed Information

Fibroblast Growth Factor 2 (FGF2) represents a vital member of the fibroblast growth factor family, distinguished by its complex structure and diverse biological functions. The protein's architecture comprises 288 amino acids, featuring a main functional domain spanning positions 143-288, while its N-terminal region (1-142) functions as a leading peptide that orchestrates protein secretion and localization. Unlike its counterpart FGF1, FGF2 employs an unconventional secretion mechanism, utilizing its unique leading peptide properties to achieve direct membrane translocation into the extracellular space rather than following the traditional endoplasmic reticulum and Golgi apparatus pathway.

Receptor Interactions and Isoform Diversity

FGF2 demonstrates remarkable molecular flexibility through its interactions with a variety of receptors, including FGFR1, FGFR2, FGFR3, and FGFR4. Additionally, it functions as an integrin ligand, binding specifically to the integrin complex ITGAV: ITGB3. This versatility is further enhanced by the existence of multiple FGF2 isoforms, which arise from alternative initiation of translation at both AUG and non-AUG (CUG) codons. These isoforms display distinct functional properties and cellular localizations, expanding the protein's range of biological effects.

Upon binding to tyrosine kinase receptors, FGF2 activates the FGF/FGFR signaling pathway, initiating a cascade of signal transduction events. This, in turn, regulates a variety of crucial biological processes, including cell proliferation, differentiation, apoptosis, and immune modulation. Notably, the JAK-STAT signaling pathway, which is integral to cartilage metabolism, is one of the key pathways influenced by FGF2.

Figure 1: FGF2 binds to tyrosine kinase receptors, activating the FGF/FGFR signaling pathway, which regulates key biological processes including cell proliferation, differentiation, apoptosis, immune response, and cartilage metabolism via the JAK-STAT pathway.Figure 1. The mechanism of action of FGF2. (Zhang J, et al., 2020)

Cellular and Developmental Functions

FGF2 is a master regulator of many cellular processes necessary for both the growth and maintenance of normal tissues in biological systems. Its impact spans basic cellular functions like survival, division, and differentiation as well as more complicated processes such as angiogenesis and tissue healing. FGF2 stimulates important developmental events including retinal lens fiber differentiation through ERK1/2 phosphorylation mediation. Its importance in tissue development and repair is especially remarkable since it promotes nervous system growth, helps to heal wounds, and maintains bone health.

Clinical Applications and Therapeutic Potential

One important area of clinical attention now is the therapeutic potential of FGF2. From encouraging tissue healing to treating degenerative diseases, its uses cut across many medical disciplines. FGF2 speeds up tissue regeneration and helps several structures—including tendons, cartilage, and bone tissue—to be repaired in wound healing. Its adaptability in therapeutic use is shown by its participation in tympanic membrane restoration and periodontal treatment.

 Role in Disease Processes and Cancer Biology

The function of the protein in disease processes, especially in cancer biology, offers both therapeutic intervention possibilities and problems. FGF2, an oncogenic agent in glioblastoma, affects tumor growth and modifies anti-tumor immunity using effects on tumor-associated macrophages. The dual character of FGF2 - encouraging both advantageous tissue regeneration and perhaps dangerous tumor growth - emphasizes the intricacy of its biological actions and the need for careful control in therapeutic uses.

Future Perspectives and Ongoing Research

Recent advances in understanding FGF2's mechanism of action have revealed its significance in cellular signaling pathways and tissue homeostasis. New facets of its function in regenerative medicine—especially in dental diseases and periodontitis treatment—are still being found by research. The capacity of the protein to stimulate tissue regeneration and cell development preserves its importance as a target for innovative therapeutic approaches across several medical disorders. As our knowledge of the multifarious functions of FGF2 in cellular processes and tissue healing deepens, its possible uses in medical therapies are growing, suggesting fresh solutions to difficult medical problems.

References:

  1. Du C, Davis JS, et al. FGF2/FGFR signaling promotes cumulus-oocyte complex maturation in vitro. Reproduction. 2021 Feb;161(2):205-214.
  2. Zhang J, Liu Z, et al. FGF2: a key regulator augmenting tendon-to-bone healing and cartilage repair. Regen Med. 2020 Sep;15(9):2129-2142.
  3. Nickle A, Ko S, et al. Fibroblast growth factor 2. Differentiation. 2024 Sep-Oct;139:100733.
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