In the weeks to come, we want to spend some time discussing someof 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 largestfamilies of growth factors. FGFs are found in nearly all multicellularlifeforms, ranging from nematodes to humans. They are crucial in the embryonicdevelopment process; responsible for developing the vascular system, CNSsystem, the mesoderm, limb development, branching morphogenesis and even brainpatterning. They are found throughout the body and phenotypic knock-out studiesof the FGF family show a large number of developmental arrests and oftenlethality.
Their function is no less important in post-embryonic growth.They continue to be responsible for vascular repair, the regulation ofelectrical excitability of cells and in the hormonal regulation of themetabolism. If that were not enough, FGF-signaling disorders have beenimplicated in a number of pathological conditions and many types of cancer. Inthe human/murine systems, there are 22 gene members of the FGF family (FGF-15and FGF-19 are orthologs of each other). They range in mass between 17-34 kDaand share 13-71% amino acid homology.
According to Itoh and Ornitz (2008), the FGF family can bebroken into 3 large subfamilies, the intracellular (iFGF) subfamily ( FGF-11/12/13/14), and two intercellularsubfamilies: 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 onany of our FGF product pages.
The iFGF family (FGF-11/12/13/14) ischaracterized as the being FGF Receptor (FGFR) independent (intracrene). Thoughthey bear a strong sequence similarity to canonical FGFs, their functional andbiochemical properties are mostly unrelated. They are important to theintracellular domains of sodium channels as well as neuronal proteins. Andunlike canonical or hFGFs, their coding region is divided by 4 introns (two ofwhich 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 targetcells far from their site of production. These FGFs play a significant role asregulatory hormones in bile acid metabolism, phosphate and Vitamin D metabolismas well as postnatal energy metabolism. The hFGF family also requires the useof co-receptors, like Klotho or βKlotho in order to activate any FGFRs,indicating that they have evolved a novel mechanism of regulation unlike any ofthe other FGF genes.
The largest FGF subfamily is the Canonical FGF family.Representing 15 FGF genes, these growth factors activate FGFRs in varyingdegrees of specificity but with a very high affinity. They are all eitherexcreted or extracellular proteins that induce dimerization and phosphorylationof specific tyrosine residues. All canonical FGFs bind in a paracrine manner toheparin and heparin sulfate and their coding region is divided by 2 introns(which are identical to the introns in the hFGFs). Canonical FGFs have essentialroles as proliferation or differentiation factors in the development of avariety of organs and tissue.
Over the next few weeks we will start to drill down into some ofthe more exciting FGF proteins and their particular stories. Stay tuned and ifyou have questions or would just like to learn more about these products,please email us at techsupport@goldbio.com!
Itoh, Nobuyuki, and David M. Ornitz. “Functionalevolutionary history of the mouse Fgf gene family.” Developmental Dynamics237.1 (2008): 18-27.
Haugsten, Ellen Margrethe, et al. “Roles of fibroblastgrowth factor receptors in carcinogenesis.” Molecular Cancer Research 8.11(2010): 1439-1452.
Itoh, Nobuyuki, and David M. Ornitz. “Fibroblast growthfactors: from molecular evolution to roles in development, metabolism anddisease.” Journal of Biochemistry 149.2 (2011): 121-130.
Coutu, Daniel L., and Jacques Galipeau. “Roles of FGFsignaling in stem cell self-renewal, senescence and aging.” Aging (AlbanyNY) 3.10 (2011): 920.
Dorey, Karel, and Enrique Amaya. “FGF signalling: diverseroles during early vertebrate embryogenesis.” Development 137.22 (2010):3731-3742.
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