Promotion and attenuation of FGF signaling through the Ras-MAPK pathway.
The fibroblast growth factors (FGFs) represent a large family of ligands that activate signal transduction pathways leading to diverse biological responses, including many involved in various processes during development. Here, we discuss the discovery of a subset of conserved FGF target genes that encode feedback regulators of FGF signaling itself. Members of the Sprouty, Sef, and mitogen-activated protein kinase phosphatase families are negative modulators of FGF signaling, whereas positive factors that promote FGF signaling include the ETS transcription factors ERM and PEA3 and the transmembrane protein XFLRT3. These molecules affect the FGF signaling cascade at different levels to regulate the final output of the pathway. This multilayered regulation suggests that precise adjustment of FGF signaling is critical in development.
Tsang
Michael
M
Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Dawid
Igor B
IB
D000818:Animals; D015536:Down-Regulation; D005346:Fibroblast Growth Factors / Q000502:physiology*; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D015854:Up-Regulation; D029867:Xenopus Proteins / Q000502:physiology
C542073:FLRT3 protein, Xenopus; D008565:Membrane Proteins; D029867:Xenopus Proteins; D005346:Fibroblast Growth Factors; D020928:Mitogen-Activated Protein Kinases; D016283:Proto-Oncogene Proteins p21(ras)