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.
The authors declare no competing or financial interests.
H.H. and Y.S. designed the research. H.H., W.-C.K., C.P.U., A.K.G., A.R. and S.R.K.V. performed the experiments. K.K., I.H., Y.I. and C.T.L. provided technical advice on the experiments. H.H., A.K.Y. and K.-H.C. analyzed the data. H.H., Y.S. and M.S. wrote the manuscript. C.T.L., Y.S. and M.S. supervised the project.
This work was supported by the National Research Foundation Singapore, under its Research Centre of Excellence, the Mechanobiology Institute.
Supplementary information available online at http://jcs.biologists.org/lookup/doi/10.1242/jcs.189415.supplemental
- Received March 15, 2016.
- Accepted August 10, 2016.
- © 2016. Published by The Company of Biologists Ltd