Rac, PAK and p38 regulate cell contact-dependent nuclear translocation of myocardin-related transcription factor

FEBS Lett. 2008 Jan 23;582(2):291-8. doi: 10.1016/j.febslet.2007.12.021. Epub 2007 Dec 27.


We investigated the mechanism whereby cell contact injury stimulates the alpha-smooth muscle actin (SMA) promoter, a key process for epithelial-mesenchymal transition (EMT) during organ fibrosis. Contact disruption by low-Ca(2+) medium (LCM) activated Rac, PAK and p38 MAPK, and triggered the nuclear accumulation of myocardin-related transcription factor (MRTF), an inducer of the SMA promoter. Dominant negative (DN) Rac, DN-PAK, DN-p38, or the p38 inhibitor SB203580 suppressed the LCM-induced nuclear accumulation of MRTF and the activation of the SMA promoter. These studies define novel pathway(s) involving Rac, PAK, and p38 in the regulation of MRTF and the contact-dependent induction of EMT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • LLC-PK1 Cells
  • Microscopy, Fluorescence
  • Nuclear Proteins / physiology*
  • Phosphorylation
  • Protein Transport
  • Swine
  • Trans-Activators / physiology*
  • Transcription Factors / metabolism*
  • p21-Activated Kinases / physiology*
  • p38 Mitogen-Activated Protein Kinases / physiology*
  • rac GTP-Binding Proteins / physiology*


  • Nuclear Proteins
  • Trans-Activators
  • Transcription Factors
  • myocardin
  • p21-Activated Kinases
  • p38 Mitogen-Activated Protein Kinases
  • rac GTP-Binding Proteins