Fibroblast Growth Factor

About Fibroblast Growth Factors:

FGF stands for Fibroblast Growth Factors, which are a family of growth factors in the body. Many of the members have similar functions and properties, while some differ too. FGF family members are normally characterized as having a role in angiogenesis, healing wounds, embryonic development and many other endocrine signaling pathways.
There has currently been a total of 22 FGF family members discovered in the human body. Every single one is structurally related to signaling molecules.

Functions
Fibroblast growth factors are a big family. As such, there is more than one function depending on that particular FGF. More often than not, these growth factors are mitogens, but they also have endocrine effects too. Many studies have referred to them as promiscuous growth factors as they have so many different functions on different cells. Four FGF receptor subtypes can be activated by over twenty different FGF ligands. As a consequence, these different functions can occur; limb development, mesoderm induction, neural development, neural induction, and anteroposterior patterning. Then, in more developed tissues/systems, additional functions such as angiogenesis, wound healing, and keratinocyte organization can occur.
Fibroblast growth factors are absolutely essential during the natural development of both vertebrates and invertebrates.
FGF1 and FGF2 are known to help promote the endothelial cell multiplication and the organization of these cells into their tube-like structure. As a result, they help promote angiogenesis and grow new blood vessels. FGF7 and FGF10 help repair injured and damaged skin/mucosal tissues.
In general, the FGF family is very important when it comes to maintenance of the brain. Therefore, it can be stated that FGFs are vital when it comes to neuronal survival throughout brain development and adult life.

Mechanism/Interactions
The FGF family has a four different receptors; FGFR1, FGFR2, FGFR3, FGFR4. These receptors of extracellular immunoglobulin-type domains (D1-D3). FGFs interact with both D2 and D3 domains. The interaction with D3 is normally what causes ligand-binding. In conjunction with this, heparan sulfate binding is also present in this domain. In between D1 and D2, you will find a small stretch of acidic amino acids. These amino acids are known to have auto-inhibitory functions.
Members of the FGF family are considered heparin-binding proteins. It is shown that they interact with cell-surface-associated heparan sulfate proteoglycans. The consequence of this is that FGF signal transduction can take place.
There is a subfamily of fibroblast growth factors on FGF19 (including FGF15, 19, 21 and 23). They’re a subfamily because they don’t bind as tightly to heparan sulfates compared to other members of the general FGF family. This results in them acting in a more endocrine fashion, which means they can affect tissues further away. They can function in the liver, kidney, bone, and intestine.

Structure
The structure of all 22 members of the FGF family differs slightly. However, it is known that FGF1 has a crystal structure. Furthermore, this structure has been solved, and there are many relations between it and interleukin 1-beta. They both contain the same beta-trefoil fold, which includes a 12-stranded beta-sheet structure. These beta-sheets are arranged around a central axis, into three similar lobes.
Generally speaking, these beta-sheets are preserved very well, which leads to the crystal structures superimposing themselves in these areas.