| 18154735 |
Sebe A, Masszi A, Zulys M, Yeung T, Speight P, Rotstein OD, Nakano H, Mucsi I, Szaszi K, Kapus A: Rac, PAK and p38 regulate cell contact-dependent nuclear translocation of myocardin-related transcription factor. FEBS Lett. 2008 Jan 23;582(2):291-8. 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. |
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