FGF Receptors

About FGF Receptors / FGFR:

FGF stands for fibroblast growth factor receptor. These are specific types of receptors that bind against different members within the fibroblast growth factor protein family. Many of these receptors are crucial elements of pathological conditions. One example of this is when FGF43 is mutated it may lead to achondroplasia.

FGF Receptors Mechanism
The FGF pathway is a key point in driving particular aspects of cellular responses. This includes responses in both malignant and normal cells. It has also been highlighted that phenotypic behaviors that are based on FGF signaling including growth and migration respond and reach maximal levels within intermediate concentrations. However, the mechanism for this has currently not been explained and high levels of FGF2 actually trigger weak responses.

FGFR Interactions
FGF is involved in a variety of interactions in the human body. For instance, one study found that it does have certain effects on the hippocampal neurons in vitro. Indeed, the study highlighted that it does cause the stimulation of neurite extension. This is true when it is bound to surfaces that have been coated with heparin sulfate, heparin or hyaluronic acid. However, it does not occur when coated with chondroitin sulfate. The study also revealed that there was a strong correlation between the rate of neurite growth and the amount of FGFR. Other studies have investigated the various interactions between retinoic acid and FGF.

FGF Receptors Function
In terms of function, FGF receptors may be involved in a range of different cancers. There are certain FRFE inhibitors that are non-selective. There are also selective FGFR inhibitors for FGFR1-4. The selective inhibitors do include, BGJ398, JN42756493 and AZD4547.
Various inhibitors are now in the early stages of clinical trials to be used to fight against the disease. It is unknown how effective this will be at this time.

FGFR Structure
The Fibroblast growth factor receptors have a number of different parts including an extracellular ligand domain. This is made up of three immunoglobulin-like domains as well as one single transmembrane helix domain. There is also an intracellular domain that is the location for tyrosine kinase activity. This is the largest family of growth factor ligands and includes 22 different members.
There are actually 48 different isoforms in FGFR. While these have various ligand-binding properties as well as kinase domains, they do share the same extracellular region. This is formed from three immunoglobulin domains. As such, it is part of the immunoglobulin superfamily.
These immunoglobulin domains provide a base for acidic amino acids. Also referred to the acid box, this can be part of the regulation of binding FGFR to FGF. The two domains DR and D2 are used for GFR binding. In certain cases, FGFs are able to activate a variety of different receptors. For instance, FGF1 is capable of binding all seven of the FGFRs. Although it is only capable of activating FGFR2b.