RhoA/Rho-associated kinase mediates fibroblast contractile force generation

The intracellular signals governing contractile force generation by non-mus cle cells remain uncertain. Our aim was to test the hypothesis that the rho A/rho-associated kinase signaling pathway is a principal mediator of contra ctile force generation in non-muscle cells, We measured myosin II regulator y light chain (MLC) phosphorylation and directly quantitated force generati on by chicken embryo fibroblasts in the absence and presence of selective i nhibitors of rhoA, and its downstream effector, rho-associated kinase, Inac tivation of rhoA, with C3 transferase, inhibited serum-stimulated MLC phosp horylation and contractile force generation. Y-27632, an inhibitor of rho-a ssociated kinase, reduced basal contractile tension, and inhibited both ser um and endothelin-1 stimulated MLC phosphorylation and contractile force ge neration. The results of this study provide novel evidence indicating that the rhoA/rho-associated kinase signaling pathway is a principal mediator of MLC phosphorylation and consequent contractile force generation by non-mus cle cells. (C) 2001 Academic Press.