In the weeks to come, we want to spend some time discussing some of our more popular and interesting growth factors and growth factor families. We begin with the Fibroblast Growth Factor family!
Fibroblast growth factors (FGFs) form one of the largest families of growth factors. FGFs are found in nearly all multicellular lifeforms, ranging from nematodes to humans. They are crucial in the embryonic development process; responsible for developing the vascular system, CNS system, the mesoderm, limb development, branching morphogenesis and even brain patterning. They are found throughout the body and phenotypic knock-out studies of the FGF family show a large number of developmental arrests and often lethality.
Their function is no less important in post-embryonic growth. They continue to be responsible for vascular repair, the regulation of electrical excitability of cells and in the hormonal regulation of the metabolism. If that were not enough, FGF-signaling disorders have been implicated in a number of pathological conditions and many types of cancer. In the human/murine systems, there are 22 gene members of the FGF family (FGF-15 and FGF-19 are orthologs of each other). They range in mass between 17-34 kDa and share 13-71% amino acid homology.
According to Itoh and Ornitz (2008), the FGF family can be broken into 3 large subfamilies, the intracellular (iFGF) subfamily ( FGF-11/12/13/14), and two intercellular subfamilies: the hormone-like (hFGF) FGF-15/21/23, and the canonical subfamilies which include the FGF-1/2/5, FGF-3/4/6, FGF-7/10/22, FGF-8/17/18 and FGF-9/16/20 subfamilies. You can find this evolutionary relationship map on any of our FGF product pages.
The iFGF family (FGF-11/12/13/14) is characterized as the being FGF Receptor (FGFR) independent (intracrene). Though they bear a strong sequence similarity to canonical FGFs, their functional and biochemical properties are mostly unrelated. They are important to the intracellular domains of sodium channels as well as neuronal proteins. And unlike canonical or hFGFs, their coding region is divided by 4 introns (two of which are identical to the other two FGF subfamilies).
The hFGF, or endocrine FGF, family (FGF-15/21/23) has low affinity for heparin-binding sites and has been found to act on target cells far from their site of production. These FGFs play a significant role as regulatory hormones in bile acid metabolism, phosphate and Vitamin D metabolism as well as postnatal energy metabolism. The hFGF family also requires the use of co-receptors, like Klotho or βKlotho in order to activate any FGFRs, indicating that they have evolved a novel mechanism of regulation unlike any of the other FGF genes.
The largest FGF subfamily is the Canonical FGF family. Representing 15 FGF genes, these growth factors activate FGFRs in varying degrees of specificity but with a very high affinity. They are all either excreted or extracellular proteins that induce dimerization and phosphorylation of specific tyrosine residues. All canonical FGFs bind in a paracrine manner to heparin and heparin sulfate and their coding region is divided by 2 introns (which are identical to the introns in the hFGFs). Canonical FGFs have essential roles as proliferation or differentiation factors in the development of a variety of organs and tissue.
Over the next few weeks we will start to drill down into some of the more exciting FGF proteins and their particular stories. Stay tuned and if you have questions or would just like to learn more about these products, please email us at firstname.lastname@example.org!
Itoh, Nobuyuki, and David M. Ornitz. "Functional evolutionary history of the mouse Fgf gene family." Developmental Dynamics 237.1 (2008): 18-27.
Haugsten, Ellen Margrethe, et al. "Roles of fibroblast growth factor receptors in carcinogenesis." Molecular Cancer Research 8.11 (2010): 1439-1452.
Itoh, Nobuyuki, and David M. Ornitz. "Fibroblast growth factors: from molecular evolution to roles in development, metabolism and disease." Journal of Biochemistry 149.2 (2011): 121-130.
Coutu, Daniel L., and Jacques Galipeau. "Roles of FGF signaling in stem cell self-renewal, senescence and aging." Aging (Albany NY) 3.10 (2011): 920.
Dorey, Karel, and Enrique Amaya. "FGF signalling: diverse roles during early vertebrate embryogenesis." Development 137.22 (2010): 3731-3742.
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