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Receptor type protein tyrosine phosphatase-kappa mediates cross-talk between transforming growth factor-beta and

Yiru Xu1, Dustin Baker, TaiHao Quan

  • 1Department of Dermatology, University of Michigan, Ann Arbor, MI 48109-5609, USA.

Molecular Biology of the Cell
|October 30, 2009
PubMed

Insights

Transforming growth factor-beta (TGF-beta) upregulates receptor-type protein tyrosine phosphatase-kappa (RPTP-kappa), which inhibits epidermal growth factor receptor (EGFR) signaling. This cross-talk integrates cell growth pathways in keratinocytes.

Area of Science:

  • Cell biology
  • Molecular signaling
  • Dermatology

Background:

  • Epidermal growth factor receptor (EGFR) signaling promotes keratinocyte proliferation.
  • Transforming growth factor-beta (TGF-beta) signaling inhibits keratinocyte proliferation.
  • Receptor-type protein tyrosine phosphatase-kappa (RPTP-kappa) dephosphorylates EGFR, blocking its signaling.

Purpose of the Study:

  • To investigate the role of RPTP-kappa in integrating EGFR and TGF-beta signaling pathways.
  • To elucidate the mechanism by which TGF-beta regulates RPTP-kappa expression and function.

Main Methods:

  • Quantitative mRNA and protein analysis to assess RPTP-kappa expression.
  • Western blotting to measure EGFR tyrosine phosphorylation.
  • shRNA to reduce RPTP-kappa levels.
  • Chromatin immunoprecipitation assays to determine transcription factor binding.

Main Results:

  • TGF-beta dose- and time-dependently upregulates RPTP-kappa mRNA and protein in human keratinocytes.
  • TGF-beta induction of RPTP-kappa decreases EGFR tyrosine phosphorylation.
  • RPTP-kappa induction by TGF-beta is dependent on Smad3 and Smad4 activation and binding to the RPTP-kappa promoter.
  • Reduced RPTP-kappa attenuates TGF-beta's anti-proliferative effects.

Conclusions:

  • RPTP-kappa acts as a key mediator integrating EGFR and TGF-beta signaling pathways.
  • TGF-beta signaling controls keratinocyte proliferation through the induction of RPTP-kappa.
  • This study reveals a novel cross-talk mechanism between growth-promoting and growth-inhibiting pathways.

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