Title |
hSef Inhibits PC-12 Cell Differentiation by Interfering with Ras-Mitogen-activated Protein Kinase MAPK Signaling*
|
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Published in |
Journal of Biological Chemistry, September 2003
|
DOI | 10.1074/jbc.m306936200 |
Pubmed ID | |
Authors |
Shiqin Xiong, Qiuhui Zhao, Zhili Rong, Guanrong Huang, Yiling Huang, Peila Chen, Shuping Zhang, Li Liu, Zhijie Chang |
Abstract |
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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 25 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 9 | 36% |
Researcher | 6 | 24% |
Student > Master | 4 | 16% |
Professor | 2 | 8% |
Other | 1 | 4% |
Other | 2 | 8% |
Unknown | 1 | 4% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 12 | 48% |
Biochemistry, Genetics and Molecular Biology | 9 | 36% |
Medicine and Dentistry | 2 | 8% |
Neuroscience | 1 | 4% |
Unknown | 1 | 4% |