Fibroblast Growth Factor Receptor ... Health Article

Definition

Fibroblast growth factor receptors (FGFRs) are a family of proteins specialized in growth inhibition. Mutations in these molecules lead to various genetic disorders involving short stature and/or premature fusion of the bones of the skull. There are at least four known FGFRs (FGFR1, FGFR2, FGFR3, FGFR4).

Description

As a group, FGFRs are very similar to each other in their structure and function. All are transmembrane proteins composed of three distinct parts. A binding site on the exterior of the cell membrane, an active site on the interior of the cell membrane, and a connecting section spanning the cell membrane and joining the inner and outer components.

Fibroblast growth factors (FGFs) attach to the binding site of extracellular portion of the FGFR protein. There are at least 17 known FGFs that bind and interact with FGFRs. Two FGFs must first bind with each other and, as a pair, are able to fit into the FGFR binding site forming an FGF/FGFR complex. FGF pairing and FGF/FGFR binding is non-specific, with any two FGFs coupling and binding any FGFR.

When the binding site is empty and no FGF is bound, the FGFR is inactive and cellular growth continues unchecked. When an FGF pair binds, the FGF/FGFR complex sends a signal that travels the length of the FGFR protein, resulting in the stimulation of the active site on the inside of the cell membrane.

The active site of the FGFR stimulates molecules within the cell through the biochemical process of phosphorylation. Each activated molecule goes on to affect another molecule, thereby propagating the original signal and, much like the domino effect, a cascade of events is triggered. The process continues, molecule by molecule, until the signal reaches the nucleus of the cell, ultimately resulting in the inhibition of cell growth.

Although highly recognized in the process of growth restriction, FGFRs are also thought to be involved in a wide variety of biological processes including migration of cells during embryo development, blood vessel growth, wound healing, cell death, and cancer.