Rac, PAK and p38 regulate cell contact-dependent nuclear translocation of myocardin-related transcription factor.
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.
D000818:Animals; D018374:LLC-PK1 Cells; D008856:Microscopy, Fluorescence; D009687:Nuclear Proteins / Q000502:physiology*; D010766:Phosphorylation; D021381:Protein Transport; D013552:Swine; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D054462:p21-Activated Kinases / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*; D020744:rac GTP-Binding Proteins / Q000502:physiology*; D000099251:Myocardin
D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D054462:p21-Activated Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020744:rac GTP-Binding Proteins; D000099251:Myocardin