FGF2

Fig1. A schematic diagram illustrating the PI(4,5)P2-dependent formation of FGF2 pores in the plasma membrane and FGF2 secretion. (David Brough, 2017)

What is FGF2 protein?

FGF2 gene (fibroblast growth factor 2) is a protein coding gene which situated on the long arm of chromosome 4 at locus 4q28. 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. The FGF2 protein is consisted of 288 amino acids and FGF2 molecular weight is approximately 30.8 kDa.

What is the function of FGF2 protein?

FGF2 is a protein with a wide range of biological functions. It is a mitogenic, angiogenic, and neurotrophic factor that is expressed at low levels in many tissues and cell types, with higher concentrations found in the brain and pituitary. FGF2 plays a role in numerous physiological and pathological processes such as limb development, angiogenesis, wound healing, and tumor growth. It is also involved in the proliferation, differentiation, and migration of various cell types of mesodermal and neuroectodermal origin . Furthermore, FGF2 is implicated in tissue repair and regeneration after injury, acting as a potent angiogenic factor and a mitogen for many cell types, including cardiomyocytes. It binds to four related tyrosine kinase receptors (FGFR1-4) and is involved in the regulation of cell growth, tissue repair, wound healing, and angiogenesis, among other functions. FGF2 also exhibits neuroprotective activity and can stimulate neurogenesis, playing a role in the central nervous system's differentiation and function.

FGF2 Related Signaling Pathway

After binding to FGFR, FGF2 can activate RAS proteins, which in turn activate RAF-1, MEK, and ERK kinases, and this cascade reaction ultimately leads to changes in gene transcription, affecting cell proliferation and differentiation. FGF2 can also activate phosphatidylinositol-3-kinase (PI3K), and then activate AKT protein, which is involved in the regulation of cell survival, proliferation and metabolism. Fgf2-activated FGFR can induce hydrolysis of phosphatidyl inositol diphosphate (PIP2) to produce inositol triphosphate (IP3) and diacylglycerol (DAG), which are second messengers that further activate protein kinase C (PKC) and other signaling molecules. FGF2 may also regulate gene expression by activating Janus kinase (JAK) and signal transducers and transcriptional activators (STAT).

FGF2 Related Diseases

FGF2 is implicated in a variety of physiological and pathological processes. It plays a crucial role in embryonic development, tissue repair, wound healing, and cell proliferation. However, dysregulation of FGF2 signaling has been associated with several diseases, including various types of cancer. Furthermore, FGF2 has been linked to Hodgkin lymphoma, where it causes aberrant signaling activities in neoplastic cells. In the context of solid tumors, FGF2 contributes to cancer progression by acting directly on tumor cells, promoting angiogenesis, and modulating the tumor microenvironment. High levels of FGF2 have also been correlated with reduced survival in cancer patients and are associated with relapse and recurrence in various cancers.

Bioapplications of FGF2

It is extensively studied for its potential in regenerative medicine, where it can stimulate the growth of new blood vessels (angiogenesis) and the healing of wounds. FGF2's ability to promote tissue regeneration makes it a candidate for therapeutic use in chronic wounds, burns, and ulcers. Additionally, its neurotrophic properties suggest applications in neurology, potentially aiding in the recovery from injuries or neurodegenerative diseases by supporting neuronal survival and growth. In the field of oncology, while FGF2's role in tumor growth is a concern, understanding its mechanisms also helps in developing targeted therapies against cancer. Moreover, FGF2's involvement in embryonic development and tissue homeostasis has made it a subject of interest in stem cell research, where it can be utilized to enhance stem cell proliferation and differentiation.