hSef potentiates EGF-mediated MAPK signaling through affecting EGFR trafficking and degradation

Yongming Ren, Long Cheng, Zhili Rong, Zhiyong Li, Yinghua Li, Xinjun Zhang, Shiqin Xiong, Jim Hu, Xin Yuan Fu, Zhijie Chang

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Sef (similar expression to fgf genes) was identified as an effective antagonist of fibroblast growth factor (FGF) in vertebrates. Previous reports have demonstrated that Sef interacts with FGF receptors (FGFRs) and inhibits FGF signaling, however, its role in regulating epidermal growth factor receptor (EGFR) signaling remains unclear. In this report, we found that hSef localizes to the plasma membrane (PM) and is subjected to rapid internalization and well localizes in early/recycling endosomes while poorly in late endosomes/lysosomes. We observed that hSef interacts and functionally colocalizes with EGFR in early endosomes in response to EGF stimulation. Importantly, we demonstrated that overexpression of hSef attenuates EGFR degradation and potentiates EGF-mediated mitogen-activated protein kinase (MAPK) signaling by interfering EGFR trafficking. Finally, our data showed that, with overexpression of hSef, elevated levels of Erk phosphorylation and differentiation of rat pheochromocytoma (PC12) cells occur in response to EGF stimulation. Taken together, these data suggest that hSef plays a positive role in the EGFR-mediated MAPK signaling pathway. This report, for the first time, reveals opposite roles for Sef in EGF and FGF signalings.

Original languageEnglish (US)
Pages (from-to)518-533
Number of pages16
JournalCellular Signalling
Volume20
Issue number3
DOIs
StatePublished - Mar 1 2008

Keywords

  • Differentiation
  • EGFR
  • Endocytosis
  • PC12 cells
  • Ras/MAPK
  • Sef

ASJC Scopus subject areas

  • Cell Biology

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    Ren, Y., Cheng, L., Rong, Z., Li, Z., Li, Y., Zhang, X., Xiong, S., Hu, J., Fu, X. Y., & Chang, Z. (2008). hSef potentiates EGF-mediated MAPK signaling through affecting EGFR trafficking and degradation. Cellular Signalling, 20(3), 518-533. https://doi.org/10.1016/j.cellsig.2007.11.010