PathFinder Cell Signaling Pathway

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FGF Pathway
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 FGF Pathway

The fibroblast growth factor (FGF) gene family is composed of 22 members, FGF-1 through FGF-23 that variously bind to seven FGF receptor isoforms from four FGF receptor genes: FGFR1b; FGFR1c; FGFR2b; FGFR2c; FGFR3b; FGFR3c and FGFR4. The b and c isoforms of FGFR1, FGFR2 and FGFR3 derive from alternative mRNA splicing that specifies the sequence of the carboxy-terminal half of each receptor’s Ig-domain III. Many of the FGF gene products also exist in multiple isoforms generated by alternative gene splicing. Fibroblast growth factors have been organized into seven subfamilies based on sequence comparisons: the FGF1 subfamily (FGF1, FGF2) contains the prototype acidic FGF and basic FGF; the FGF4 subfamily (FGF4, FGF6, FGF5); the FGF7 (keratinocyte growth factor, KGF) subfamily (FGF3, FGF7, FGF10, FGF22); the FGF8 subfamily (FGF8, FGF17 and FGF18); the FGF9 subfamily (FGF9, FGF16, FGF29); the FGF11 subfamily (FGF11, FGF12, FGF13 and FGF14), originally the FGF homologous factors (FHF) 1–4 family (FHF1–FHF4) and the FGF19 subfamily (FGF19, FGF,21 and FGF23).

Fibroblast growth factor binding induces receptor tyrosine kinase (RTK) dimerization and activation leading to the activation of a plethora of signaling pathways involved with cell growth, differentiation and functions important for normal development, tissue maintenance and would repair. Activation of specific cell signaling pathways is dependent upon the interaction of specific FGF ligands and FGF receptors and cell context. Effective activation of extracellular FGF signaling typically (except the FGF11 subfamily) requires the association of FGF and the FGF receptor with the extracellular matrix through components such as heparan sulfate glycosaminoglycans (HS). In addition to cell surface signaling, some FGF:FGF receptor complexes are translocated to the nucleus where they signal gene expression. Recent work suggests that some FGF isoforms may function as nuclear signaling factors without ever being secreted.

References:

  1. Lee, P.L. et. al. (1989) Purification and complementary DNA cloning of a receptor for basic fibroblast growth factor. Science. 245, 57–60.
  2. Mignatti, P. et. al. (1992) Basic fibroblast growth factor, a protein devoid of secretory signal sequence, is released by cells via a pathway independent of the endoplasmic reticulum-Golgi complex. J. Cell Physiol. 151, 81–93.
  3. Miki, T. et. al. (1992) Determination of ligand-binding specificity by alternative splicing: two distinct growth factor receptors encoded by a single gene. Proc. Natl. Acad. Sci. USA. 89, 246–250.
  4. Gringel, S. et. al. (2004) Nuclear fibroblast growth factor-2 interacts specifically with splicing factor SF3a66. J. Biol. Chem. 385, 1203-1208.
  5. Ornitz, D.M. and Itoh, N. (2001) Fibroblast growth factors. Genome Biol. 2, 1-12.
  6. Sorensen, V. et. al. (2006) Functional diversity of FGF-2 isoforms by intracellular sorting. Bioessays. 28, 504-514.

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Content for this page is provided by Dennis R. Conrad, Ph.D., a Life Science industry consultant with over 25 years of experience in the formulation and optimization of cell culture media. Dr. Conrad's email address is biomediaexpert@earthlink.net