MEKK1-dependent phosphorylation of calponin-3 tunes cell contractility.
Hiroaki Hirata, Wei-Chi Ku, Ai Kia Yip, Chaitanya Prashant Ursekar, Keiko Kawauchi, Amrita Roy, Alvin Kunyao Guo, Sri Ram Krishna Vedula, Ichiro Harada, Keng-Hwee Chiam, Yasushi Ishihama, Chwee Teck Lim, Yasuhiro Sawada, Masahiro Sokabe
Author Information
Hiroaki Hirata: Mechanobiology Institute, National University of Singapore, 117411 Singapore. ORCID
Wei-Chi Ku: Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
Ai Kia Yip: A*STAR Bioinformatics Institute, 138671 Singapore.
Chaitanya Prashant Ursekar: Mechanobiology Institute, National University of Singapore, 117411 Singapore. ORCID
Keiko Kawauchi: Mechanobiology Institute, National University of Singapore, 117411 Singapore.
Amrita Roy: Mechanobiology Institute, National University of Singapore, 117411 Singapore.
Alvin Kunyao Guo: Mechanobiology Institute, National University of Singapore, 117411 Singapore.
Sri Ram Krishna Vedula: Mechanobiology Institute, National University of Singapore, 117411 Singapore.
Ichiro Harada: Locomotive Syndrome Research Institute, Nadogaya Hospital, Kashiwa 277-0032, Japan Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
Keng-Hwee Chiam: Mechanobiology Institute, National University of Singapore, 117411 Singapore A*STAR Bioinformatics Institute, 138671 Singapore.
Yasushi Ishihama: Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
Chwee Teck Lim: Mechanobiology Institute, National University of Singapore, 117411 Singapore Department of Biomedical Engineering, National University of Singapore, 117583 Singapore.
Yasuhiro Sawada: Mechanobiology Institute, National University of Singapore, 117411 Singapore Locomotive Syndrome Research Institute, Nadogaya Hospital, Kashiwa 277-0032, Japan Department of Biological Sciences, National University of Singapore, 117543 Singapore ys454-ind@umin.ac.jp msokabe@med.nagoya-u.ac.jp.
Masahiro Sokabe: Mechanobiology Institute, National University of Singapore, 117411 Singapore Mechanobiology Laboratory, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan ys454-ind@umin.ac.jp msokabe@med.nagoya-u.ac.jp. ORCID
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.
