hSef inhibits PC-12 cell differentiation by interfering with Ras-mitogen-activated protein kinase MAPK signaling.
Growth factor signaling by receptor tyrosine kinases regulates several cell fates, such as proliferation and differentiation. Sef was genetically identified as a negative regulator of fibroblast growth factor (FGF) signaling. Using bioinformatic methods and rapid amplification of cDNA ends-PCR, we isolated both the mouse and the human Sef genes, which ... encoded the Sef protein and Sef-S isoform that was generated through alternative splicing. We provide evidence that the Sef gene products were located mainly on the cell membrane. Co-immunoprecipitation and immunostaining experiments indicate that hSef interacts with FGFR1 and FGFR2 but not FGFR3. Our results demonstrated that stably expressed hSef strongly inhibits FGF2- or nerve growth factor-induced PC-12 cell differentiation. The intracellular domain of hSef is necessary for the inhibitory effect on FGF2-induced PC-12 cell differentiation. Furthermore, our data suggested Sef exerted the negative effect on FGF2-induced PC-12 cell differentiation through the prevention of Ras-mitogen-activated protein kinase signaling, possibly functioning upstream of the Ras molecule. These findings suggest that Sef may play an important role in the regulation of PC-12 cell differentiation.
Mesh Terms:
Alternative Splicing, Amino Acid Sequence, Animals, Base Sequence, COS Cells, Cell Differentiation, Cell Division, Cell Line, Cloning, Molecular, DNA, Complementary, Dose-Response Relationship, Drug, Fibroblast Growth Factor 2, Fibroblast Growth Factors, Humans, Luciferases, MAP Kinase Signaling System, Mice, Microscopy, Fluorescence, Models, Genetic, Molecular Sequence Data, PC12 Cells, Plasmids, Precipitin Tests, Protein Isoforms, Rats, Receptors, Interleukin, Sequence Homology, Amino Acid, Signal Transduction, Time Factors, Transfection, ras Proteins
Alternative Splicing, Amino Acid Sequence, Animals, Base Sequence, COS Cells, Cell Differentiation, Cell Division, Cell Line, Cloning, Molecular, DNA, Complementary, Dose-Response Relationship, Drug, Fibroblast Growth Factor 2, Fibroblast Growth Factors, Humans, Luciferases, MAP Kinase Signaling System, Mice, Microscopy, Fluorescence, Models, Genetic, Molecular Sequence Data, PC12 Cells, Plasmids, Precipitin Tests, Protein Isoforms, Rats, Receptors, Interleukin, Sequence Homology, Amino Acid, Signal Transduction, Time Factors, Transfection, ras Proteins
J. Biol. Chem.
Date: Dec. 12, 2003
PubMed ID: 12958313
View in: Pubmed Google Scholar
Download Curated Data For This Publication
211531
Switch View:
- Interactions 2