Glia-activating factor is a protein that in humans is encoded by the FGF9 gene. [5] [6]
Glia-activating factor is a protein that in humans is encoded by the FGF9 gene. [5] [6]
The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This protein was isolated as a secreted factor that exhibits a growth-stimulating effect on cultured glial cells. In nervous system, this protein is produced mainly by neurons and may be important for glial cell development. Expression of the mouse homolog of this gene was found to be dependent on Sonic hedgehog (Shh) signaling. Mice lacking the homolog gene displayed a male-to-female sex reversal phenotype, which suggested a role in testicular embryogenesis. [6] This gene is involved in the patterning of sex determination, lung development, and skeletal development.
FGF9 has also been shown to play a vital role in male sex development. FGF9’s role in sex determination begins with its expression in the bi-potent gonads for both females and males. [7] Once activated by SOX9, it is responsible for forming a feedforward loop with Sox9, increasing the levels of both genes. It forms a positive feedback loop upregulating SOX9, while simultaneously inactivating the female Wnt4 signaling pathway. [7] [8]
In lung development, FGF9 is expressed in the mesothelium and pulmonary epithelium, where its purpose is to retain lung mesenchymal proliferation. Inactivation of FGF9 results in diminished epithelial branching. [9] By the end of gestation, the lungs that are developed cannot sustain life and will result in a prenatal death. [9]
Another biological role presented by this gene is its involvement in skeletal development and repair. FGF9 and FGF18 both stimulate chondrocyte proliferation. [10] FGF9 heterozygous mutant mice had a compromised bone repair after an injury with less expression of VEGF and VEGFR2 and lower osteoclast recruitment. [10] One disease associated with this gene is multiple synostoses syndrome (SYNS), a rare bone disease that has to do with the fusion of the fingers and toes. [11] A missense mutation in the second exon of the FGF9 gene, the S99N mutation, seems to be the third cause of SYNS. [12] A mutation in Noggin (NOG) and the Growth Differentiation Factor 5 (GDF5) are the other two causes of SYNS. [12] The S99N mutation results in cell signaling irregularities that interfere with chondrogenesis and osteogenesis causing the fusion of the joints during development. [12]
FGF9 is a gene within the larger family of fibroblast growth factors (FGF), a type of cell signaling protein. This gene signals embryonic stem cell development and sex determination. FGF9 gene expression is also essential for development of the prostate and maintaining prostate tissue homeostasis. The prostate is a male reproductive organ that is composed of epithelial and stromal cells. Overexpression of FGF9 in prostate epithelial cells can lead to high grade prostate intraepithelial neoplasia, which is a precursor for prostate cancer. Additionally, high expression of the gene in prostate epithelial cells disrupts prostate tissue homeostasis, and promotes a high frequency of metastasis. On the other hand, overexpression of FGF9 in the alternate, prostate stromal cells, promotes the communication with prostate cancer cells.
It has been reported that abnormal expression of FGF9 has oncogenic effects in various human cancers including; ovarian, brain, lung, and colon cancers. In studies with mice, high expression of FGF9 resulted in fusion of the prostate and seminal vesicles, and penis protrusion. More importantly, it caused hyperplasia in both stromal and epithelial compartments. Due to the enlargement of tissue caused by an increase in the reproduction rate of its cells, hyperplasia is frequently the primary stage in the development of cancer.
Although several studies have proven that high expression of FGF9 correlates to the progression of prostate cancer, the question of whether overexpression of FGF9 initiates prostate tumorigenesis is still being tested.
FGF9 has been shown to interact with Fibroblast growth factor receptor 3. [13] [14]
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The epidermal growth factor receptor is a transmembrane protein that is a receptor for members of the epidermal growth factor family of extracellular protein ligands.
Fibroblast growth factor 1, (FGF-1) also known as acidic fibroblast growth factor (aFGF), is a growth factor and signaling protein encoded by the FGF1 gene. It is synthesized as a 155 amino acid polypeptide, whose mature form is a non-glycosylated 17-18 kDa protein. Fibroblast growth factor protein was first purified in 1975, but soon afterwards others using different conditions isolated acidic FGF, Heparin-binding growth factor-1, and Endothelial cell growth factor-1. Gene sequencing revealed that this group was actually the same growth factor and that FGF1 was a member of a family of FGF proteins.
INT-2 proto-oncogene protein also known as FGF-3 is a protein that in humans is encoded by the FGF3 gene.
The fibroblast growth factor receptors (FGFR) are, as their name implies, receptors that bind to members of the fibroblast growth factor (FGF) family of proteins. Some of these receptors are involved in pathological conditions. For example, a point mutation in FGFR3 can lead to achondroplasia.
Fibroblast growth factor receptor 2 (FGFR2) also known as CD332 is a protein that in humans is encoded by the FGFR2 gene residing on chromosome 10. FGFR2 is a receptor for fibroblast growth factor.
Fibroblast growth factor receptor 1 (FGFR1), also known as basic fibroblast growth factor receptor 1, fms-related tyrosine kinase-2 / Pfeiffer syndrome, and CD331, is a receptor tyrosine kinase whose ligands are specific members of the fibroblast growth factor family. FGFR1 has been shown to be associated with Pfeiffer syndrome, and clonal eosinophilias.
Fibroblast growth factor receptor 4 is a protein that in humans is encoded by the FGFR4 gene. FGFR4 has also been designated as CD334.
Sprouty homolog 2 (Drosophila), also known as SPRY2, is a protein which in humans is encoded by the SPRY2 gene.
Kruppel-like factor 4 is a member of the KLF family of zinc finger transcription factors, which belongs to the relatively large family of SP1-like transcription factors. KLF4 is involved in the regulation of proliferation, differentiation, apoptosis and somatic cell reprogramming. Evidence also suggests that KLF4 is a tumor suppressor in certain cancers, including colorectal cancer. It has three C2H2-zinc fingers at its carboxyl terminus that are closely related to another KLF, KLF2. It has two nuclear localization sequences that signals it to localize to the nucleus. In embryonic stem cells (ESCs), KLF4 has been demonstrated to be a good indicator of stem-like capacity. It is suggested that the same is true in mesenchymal stem cells (MSCs).
Keratinocyte growth factor is a protein that in humans is encoded by the FGF7 gene.
Fibroblast activation protein alpha (FAP-alpha) also known as prolyl endopeptidase FAP is an enzyme that in humans is encoded by the FAP gene.
Fibroblast growth factor 10 is a protein that in humans is encoded by the FGF10 gene.
Fibroblast growth factor 8(FGF-8) is a protein that in humans is encoded by the FGF8 gene.
Fibroblast growth factor 4 is a protein that in humans is encoded by the FGF4 gene.
Fibroblast growth factor 5 is a protein that in humans is encoded by the FGF5 gene.
Fibroblast growth factor 18 (FGF18) is a protein that is encoded by the Fgf18 gene in humans. The protein was first discovered in 1998, when two newly-identified murine genes Fgf17 and Fgf18 were described and confirmed as being closely related by sequence homology to Fgf8. The three proteins were eventually grouped into the FGF8 subfamily, which contains several of the endocrine FGF superfamily members FGF8, FGF17, and FGF18. Subsequent studies identified FGF18's role in promoting chondrogenesis, and an apparent specific activity for the generation of the hyaline cartilage in articular joints.
Fibroblast growth factor 19 is a protein that in humans is encoded by the FGF19 gene. It functions as a hormone, regulating bile acid synthesis, with effects on glucose and lipid metabolism. Reduced synthesis, and blood levels, may be a factor in chronic bile acid diarrhea and in certain metabolic disorders.
Fibroblast growth factor 6 is a protein that in humans is encoded by the FGF6 gene.
Fibroblast growth factor 17 is a protein that in humans is encoded by the FGF17 gene.
Fibroblast growth factor 22 is a protein which in humans is encoded by the FGF22 gene.
