PMC

Open configuration of active ROCK is mediated by binding of RhoA to the Rho binding domain (RBD), cleavage of the carboxy pleckstrin homology (PH) domain by caspase 3, or binding of arachidonic acid to the PH domain.

Activation of ROCK by GTP-bound RhoA inhibits myosin light chain phosphatase (MLCP) leading to increased MLC phosphorylation and stress fiber formation. ROCK can also activate LIM kinase, leading to phosphorylation of cofilin, actin nucleation and polymerization. GEF, guanine exchange factor; GAP, GTPase-activating protein; MLC, myosin light chain; MLCK, MLC kinase; p, phosphorylation.

Both of the isoforms (ROCK1 and ROCK 2) consist of an amino-terminal kinase domain followed by a coiled-coil forming region containing a Rho-binding (RB) domain and a carboxy-terminal cysteine-rich domain (CRD) located within the pleckstrin-homology (PH). The isoforms share overall 65% homology in amino acid sequence and 92% homology in their kinase domains. (adapted with permission from Rikitake R. and Liao J.K. (2005) Expert Rev Cardiovasc Ther 3:441–451, Expert Reviews Ltd.)