Rac、PAK和p38调节细胞接触依赖性心肌相关转录因子的核转位。
Rac, PAK and p38 regulate cell contact-dependent nuclear translocation of myocardin-related transcription factor.
作者信息
Sebe Attila, Masszi András, Zulys Matthew, Yeung Tony, Speight Pam, Rotstein Ori D, Nakano Hiroyasu, Mucsi István, Szászi Katalin, Kapus András
机构信息
Keenan Research Centre, Li Ka Shing Knowledge Institute of St. Michael's Hospital, 30 Bond Street, Toronto, Ontario, Canada.
出版信息
FEBS Lett. 2008 Jan 23;582(2):291-8. doi: 10.1016/j.febslet.2007.12.021. Epub 2007 Dec 27.
Abstract
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.
摘要
我们研究了细胞接触损伤刺激α-平滑肌肌动蛋白（SMA）启动子的机制，这是器官纤维化过程中上皮-间质转化（EMT）的关键过程。低钙（2+）培养基（LCM）导致的接触中断激活了Rac、PAK和p38丝裂原活化蛋白激酶（MAPK），并触发了心肌素相关转录因子（MRTF）的核内积聚，MRTF是SMA启动子的诱导剂。显性负性（DN）Rac、DN-PAK、DN-p38或p38抑制剂SB203580抑制了LCM诱导的MRTF核内积聚和SMA启动子的激活。这些研究确定了涉及Rac、PAK和p38的新途径，这些途径参与了MRTF的调节以及EMT的接触依赖性诱导。
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