Fibroblast growth factors (FGFs) and one of the cognate receptors, FGFR4, are implicated in liver development and function. However, Yu et al. report that in mice lacking FGFR4, it is not the liver that appears abnormal, but the gall bladder, which is much smaller in size. FGFR4 deficiency resulted in elevated bile acid pools. This elevation correlated with increased expression of Cyp7α, an enzyme that synthesizes bile acids from cholesterol. The authors suggest that FGFR4 negatively regulates bile acid synthesis by repressing Cyp7α expression. This may occur through activation of RIP140, a corepressor of the oxysterol receptor LXRα, which itself is an activator of Cyp7α. Hence, a transmembrane receptor tyrosine kinase could maintain cholesterol and bile acid homeostasis by communicating changes in tissue microenvironment to a metabolite-controlled transcription network.
Yu, C., Wang, F., Kan, M., Jin, C., Jones, R.B., Weinstein, M., Deng, C.-X., and McKeehan, W.L. (2000) Elevated cholesterol metabolism and bile acid synthesis in mice lacking membrane tyrosine kinase receptor FGFR4. J. Biol. Chem. 275: 15482-15489. [Abstract] [Full Text]