Abstract
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
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Active Transport, Cell Nucleus / physiology
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Amino Acid Sequence
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Animals
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Axin Protein
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Cell Differentiation / physiology*
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Cell Line
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Cell Nucleus / metabolism
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Cell Shape
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DEAD-box RNA Helicases / genetics
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DEAD-box RNA Helicases / metabolism*
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Epithelial Cells / cytology
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Epithelial Cells / physiology*
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Humans
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Mesoderm / cytology*
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Mesoderm / physiology
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Molecular Sequence Data
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Phosphorylation
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Platelet-Derived Growth Factor / metabolism*
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Proto-Oncogene Proteins c-abl / metabolism
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Signal Transduction / physiology
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T Cell Transcription Factor 1 / genetics
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T Cell Transcription Factor 1 / metabolism
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Tyrosine / metabolism
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Wnt Proteins / metabolism
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beta Catenin / genetics
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beta Catenin / metabolism*
Substances
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Axin Protein
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Platelet-Derived Growth Factor
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RNA, Small Interfering
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Repressor Proteins
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T Cell Transcription Factor 1
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Wnt Proteins
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beta Catenin
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Tyrosine
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Proto-Oncogene Proteins c-abl
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DEAD-box RNA Helicases