Figure 2.

Upstream and downstream regulation of ROCK. Activation of G protein-coupled receptors, e.g., AT1 or ET-1, or receptors for cytokines or other growth factors, activate RhoGEF that, in turn phosphorylates RhoA/ROCK. The major ROCK downstream pathways are (1) myosin light chain phosphatase (MLCP)/MLC, (2) ezrin, radixin and moesin (ERM), (3) myocardin and serum response factor (SRF), (4) LIM (Lin-11, Isl-1,Mec-3))/cofilin, (5) assembly of F-actin with release of myocardin-related transcription factor (MRTF). The assembly of F-actin enables MRTF to dissociate from G-actin, leading to MRTF nuclear translocation and binding to SRF, which triggers transcription of genes involved in cardiovascular remodeling. However, all pathways concur to the development of smooth muscle cell proliferation, transition of myocytes into myofibroblasts and fibrosis, or stress fibers formation.