Fig. 2 Increased ECM stiffness activates the Rho-mediated cell contractility pathway. Increased ECM stiffness activates the Rho-mediated cell contractility.

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Fig. 2 Increased ECM stiffness activates the Rho-mediated cell contractility pathway. Increased ECM stiffness activates the Rho-mediated cell contractility pathway. Mechanical force on integrins activates the Rho guanine nucleotide exchange factors (GEFs), GEF-H1 and LARG, to catalyze the exchange of guanosine diphosphate (GDP) for GTP. The major Rho effector Rho-associated kinase (ROCK) induces actomyosin cell contractility by phosphorylating myosin light chain phosphatase (MLCP) and myosin light chain (MLC). Downstream of Rho activation, myocardin-related transcription factor A (MRTF-A), yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ), nuclear factor κB (NF-κB), and mitogen-activated protein kinase (MAPK) pathways regulate gene expression, and Rho activity has pathological implications on cell survival, migration, proliferation, and ECM synthesis. Solid arrows indicate direction of cellular traction force generation (blue) and Rho-mediated contractility pathway events (black). Dashed black arrows represent cellular responses downstream of Rho-mediated cell contractility. Marsha C. Lampi and Cynthia A. Reinhart-King Sci Transl Med 2018;10:eaao0475 Published by AAAS