MEKK1-dependent phosphorylation of calponin-3 tunes cell contractility
MEKK1-dependent phosphorylation of calponin-3 tunes cell contractility
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DOI：
10.1242/jcs.189415
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发表时间：
2016-10-01
影响因子：
4
通讯作者：
Sokabe, Masahiro
中科院分区：
文献类型：
--
作者：
Hirata, Hiroaki;Ku, Wei-Chi;Sokabe, Masahiro
MEKK 1（也称为MAP 3 K1）在MAPK信号传导中起主要作用，与细胞中的机械过程（如迁移）有关。在这里，我们确定肌动蛋白结合蛋白calponin-3作为一个新的MEKK 1底物的信号调节肌动球蛋白为基础的细胞收缩。MEKK 1与肌动蛋白细胞骨架上的钙调蛋白-3共定位并使其磷酸化，导致细胞产生的牵引应力增加。MEKK 1介导的钙调蛋白-3磷酸化通过抑制肌球蛋白II活性、破坏肌动蛋白细胞骨架完整性和粘附于软的细胞外基质而减弱，而在细胞拉伸时增强。我们的研究结果揭示了MEKK 1-calponin-3信号通路对细胞收缩性的重要性。
MEKK1 (also known as MAP3K1), which plays a major role in MAPK signaling, has been implicated in mechanical processes in cells, such as migration. Here, we identify the actin-binding protein calponin-3 as a new MEKK1 substrate in the signaling that regulates actomyosin-based cellular contractility. MEKK1 colocalizes with calponin-3 at the actin cytoskeleton and phosphorylates it, leading to an increase in the cell-generated traction stress. MEKK1-mediated calponin-3 phosphorylation is attenuated by the inhibition of myosin II activity, the disruption of actin cytoskeletal integrity and adhesion to soft extracellular substrates, whereas it is enhanced upon cell stretching. Our results reveal the importance of the MEKK1-calponin-3 signaling pathway to cell contractility.