Functional Diversity of Fibroblast Growth Factors in Bone Formation

Figure 1

FGF/FGFR signaling and its feedback loops. Ligand-dependent activation of FGFR tyrosine kinases induces ERK1/2, p38 MAPK, and Akt phosphorylation and subsequent upregulation of their downstream transcriptional factors such as early growth response protein-1 (Egr-1), activating transcriptional factor- (ATF-) 2, and mammalian target of rapamycin (mTOR). These transcription factors regulate the expression of genes involved in osteoblastogenesis. Canopy1 acts as positive feedback factor for FGF/FGFR signaling. Sef and Spry4 silence FGF/FGFR signaling. pTKs: phosphorylated tyrosine kinases; PLCγ: phospholipase C γ; PKC: protein kinase C; MEK: mitogen-activated protein kinase; PI3 K: phosphoinositide 3-kinase.