title: MEKK1-dependent phosphorylation of calponin-3 tunes cell contractility.
abstract: 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.
authors.affiliation: Mechanobiology Institute, National University of Singapore, 117411 Singapore.
authors.forename: Hiroaki
authors.identifier: 0000-0002-2604-9158
authors.initials: H
authors.lastname: Hirata
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Wei-Chi
authors.initials: WC
authors.lastname: Ku
authors.affiliation: A*STAR Bioinformatics Institute, 138671 Singapore.
authors.forename: Ai Kia
authors.initials: AK
authors.lastname: Yip
authors.affiliation: Mechanobiology Institute, National University of Singapore, 117411 Singapore.
authors.forename: Chaitanya Prashant
authors.identifier: 0000-0001-9253-0559
authors.initials: CP
authors.lastname: Ursekar
authors.affiliation: Mechanobiology Institute, National University of Singapore, 117411 Singapore.
authors.forename: Keiko
authors.initials: K
authors.lastname: Kawauchi
authors.affiliation: Mechanobiology Institute, National University of Singapore, 117411 Singapore.
authors.forename: Amrita
authors.initials: A
authors.lastname: Roy
authors.affiliation: Mechanobiology Institute, National University of Singapore, 117411 Singapore.
authors.forename: Alvin Kunyao
authors.initials: AK
authors.lastname: Guo
authors.affiliation: Mechanobiology Institute, National University of Singapore, 117411 Singapore.
authors.forename: Sri Ram Krishna
authors.initials: SR
authors.lastname: Vedula
authors.affiliation: Locomotive Syndrome Research Institute, Nadogaya Hospital, Kashiwa 277-0032, Japan Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Harada
authors.affiliation: Mechanobiology Institute, National University of Singapore, 117411 Singapore A*STAR Bioinformatics Institute, 138671 Singapore.
authors.forename: Keng-Hwee
authors.initials: KH
authors.lastname: Chiam
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ishihama
authors.affiliation: Mechanobiology Institute, National University of Singapore, 117411 Singapore Department of Biomedical Engineering, National University of Singapore, 117583 Singapore.
authors.forename: Chwee Teck
authors.initials: CT
authors.lastname: Lim
authors.affiliation: 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.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Sawada
authors.affiliation: 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.
authors.forename: Masahiro
authors.identifier: 0000-0001-7791-0166
authors.initials: M
authors.lastname: Sokabe
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D001696:Biomechanical Phenomena; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D048728:MAP Kinase Kinase Kinase 1 / Q000378:metabolism*; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D024462:Myosin Type II / Q000378:metabolism; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D010769:Phosphothreonine / Q000378:metabolism; D013312:Stress, Physiological; D000096985:Calponins
chemical_list: D002135:Calcium-Binding Proteins; D048728:MAP Kinase Kinase Kinase 1; D008840:Microfilament Proteins; D024462:Myosin Type II; D010769:Phosphothreonine; D000096985:Calponins; C482578:Map3k1 protein, mouse
keywords: Actomyosin; Mechanotransduction; Phosphorylation; Substrate rigidity