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Rac, PAK and p38 regulate cell contact‐dependent nuclear translocation of myocardin‐related transcription factor
Author(s) -
Sebe Attila,
Masszi András,
Zulys Matthew,
Yeung Tony,
Speight Pam,
Rotstein Ori. D.,
Nakano Hiroyasu,
Mucsi István,
Szászi Katalin,
Kapus András
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.12.021
Subject(s) - myocardin , serum response factor , transcription factor , microbiology and biotechnology , p38 mitogen activated protein kinases , chemistry , transcription (linguistics) , biology , mapk/erk pathway , signal transduction , biochemistry , gene , linguistics , philosophy
We investigated the mechanism whereby cell contact injury stimulates the α‐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.