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hSef inhibits PC-12 cell differentiation by interfering with Ras-mitogen-activated protein kinase MAPK signaling

Shiqin Xiong1, Qiuhui Zhao, Zhili Rong

  • 1Tsinghua Institute of Genome Research, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084,China.

The Journal of Biological Chemistry
|September 6, 2003
PubMed

Insights

Sef protein negatively regulates cell differentiation by inhibiting fibroblast growth factor (FGF) signaling pathways. This study identifies Sef

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Signal Transduction

Background:

  • Receptor tyrosine kinases mediate growth factor signaling, controlling cell proliferation and differentiation.
  • Sef was previously identified as a negative regulator of fibroblast growth factor (FGF) signaling.

Purpose of the Study:

  • To isolate and characterize mouse and human Sef genes and their protein products.
  • To investigate the role of Sef in regulating PC-12 cell differentiation and FGF signaling.

Main Methods:

  • Bioinformatic analysis and rapid amplification of cDNA ends-PCR for gene isolation.
  • Co-immunoprecipitation and immunostaining to determine protein interactions and localization.
  • Stable expression of human Sef (hSef) in PC-12 cells to assess functional effects.

Main Results:

  • Mouse and human Sef genes were isolated, encoding Sef protein and an alternative splice isoform (Sef-S).
  • Sef protein localizes to the cell membrane and interacts with FGFR1 and FGFR2.
  • hSef inhibits FGF2- or nerve growth factor-induced PC-12 cell differentiation, requiring its intracellular domain and potentially acting upstream of Ras-MAPK signaling.

Conclusions:

  • Sef acts as a negative regulator of PC-12 cell differentiation.
  • Sef's inhibitory mechanism involves interfering with Ras-mitogen-activated protein kinase signaling.
  • Sef plays a significant role in modulating cell differentiation processes.

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