In all of our recent talk about growth factors, let us not forget that, in nature, growth factors are only ever half of the equation. Receptors are proteins which are often found in the plasma membrane of a cell that receive chemical signals (molecular binding) from outside of the cell and direct the cell to do something specific; such as dividing, dying or allowing transmembrane transportation. Typically, growth factor receptors use one of three pathways: JAK/STAT, MAP Kinase or PI3 Kinase.

Nearly all of the 22 Fibroblast Growth Factors (FGFs) that exist in humans bind to one of four FGF Receptors (FGFRs). The FGFRs are single-pass transmembrane receptors which help to tightly regulate the FGF signaling (along with heparan sulfate) by means of their binding specificity. The FGFRs are composed of three immunoglobulin-like (Ig) domains (D1-D3), which are involved in ligand interaction, a single transmembrane helix domain, a string of acidic residues between the first and second Ig domain and an intracellular domain with tyrosine kinase activity (Givol, 1992). Further, the D3 domain may have alternative splicing between its exons (see picture), resulting in two additional isoforms; b and c. The combination of these four basic receptors and their isoforms result in 7 principle FGFRs: FGFR1c, FGFR1b, FGFR2c, FGFR2b, FGFR3c, FGFR3b, and FGFR4.

The FGFRs are capable of binding to more than one FGF, and most FGFs are capable of binding to more than one FGFR (although there is usually a preferred interaction). The alternative splicing of the D3 domain restricts the ligand specificity of FGFR1b-3b to mesenchymally expressed FGFs and that of FGFR1c-3c to epithelially expressed FGFs (Beenken, 2012). Interestingly, FGF1 (or acidic FGF) is the only FGF that appears to have no specific binding preferences, binding equally well with both the “b” and “c” isoforms! Beenken et al., researched into the underlying plasticity of FGF1, and discovered that the N-terminal region was the key determinant of its receptor binding promiscuity (and in fact that the N-terminal region is also the key determinant in most FGF’s specificity) as opposed to the interface of its core and the alternatively spliced βC’-βE and βF-βG loops of the D3 region of the receptor. For a more in-depth read of their fascinating research, you can read it online at The Journal of Biological Chemistry. And if you have any questions about our available growth factors, or any of our products, just email us at!

Givol, D., & Yayon, A. (1992). Complexity of FGF receptors: genetic basis for structural diversity and functional specificity. The FASEB journal, 6(15), 3362-3369.

Beenken, Andrew, et al. (2012). Plasticity in Interactions of Fibroblast Growth Factor 1 (FGF1) N Terminus with FGF Receptors Underlies Promiscuity of FGF1. Journal of Biological Chemistry, 287(5), 3067-3078.

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