P68 RNA helicase mediates PDGF-induced epithelial mesenchymal transition by displacing Axin from beta-catenin

Cell. 2006 Oct 6;127(1):139-55. doi: 10.1016/j.cell.2006.08.036.


The nuclear p68 RNA helicase (referred to as p68) is a prototypical member of the DEAD box family of RNA helicases. The protein plays a very important role in early organ development. In the present study, we characterized the tyrosine phosphorylation of p68 under platelet-derived growth factor (PDGF) stimulation. We demonstrated that tyrosine phosphorylation of p68 at Y593 mediated PDGF-stimulated epithelial-mesenchymal transition (EMT). We showed that PDGF treatment led to phosphorylation of p68 at Y593 in the cell nucleus. The Y593-phosphorylated p68 (referred to as phosphor-p68) promotes beta-catenin nuclear translocation via a Wnt-independent pathway. The phosphor-p68 facilitates beta-catenin nuclear translocation by blocking phosphorylation of beta-catenin by GSK-3beta and displacing Axin from beta-catenin. The beta-catenin nuclear translocation and subsequent interaction with the LEF/TCF was required for the EMT process. These data demonstrated a novel mechanism of phosphor-p68 in mediating the growth factor-induced EMT and uncovered a new pathway to promote beta-catenin nuclear translocation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / physiology
  • Amino Acid Sequence
  • Animals
  • Axin Protein
  • Cell Differentiation / physiology*
  • Cell Line
  • Cell Nucleus / metabolism
  • Cell Shape
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism*
  • Epithelial Cells / cytology
  • Epithelial Cells / physiology*
  • Humans
  • Mesoderm / cytology*
  • Mesoderm / physiology
  • Molecular Sequence Data
  • Phosphorylation
  • Platelet-Derived Growth Factor / metabolism*
  • Proto-Oncogene Proteins c-abl / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Signal Transduction / physiology
  • T Cell Transcription Factor 1 / genetics
  • T Cell Transcription Factor 1 / metabolism
  • Tyrosine / metabolism
  • Wnt Proteins / metabolism
  • beta Catenin / genetics
  • beta Catenin / metabolism*


  • Axin Protein
  • Platelet-Derived Growth Factor
  • RNA, Small Interfering
  • Repressor Proteins
  • T Cell Transcription Factor 1
  • Wnt Proteins
  • beta Catenin
  • Tyrosine
  • Proto-Oncogene Proteins c-abl
  • DEAD-box RNA Helicases