ROCK (Rho-associated kinase), a family of serine/threonine kinases, is an important downstream target of Rho-GTPase and plays an important role in Rho-mediated signaling. Two isoforms of ROCK have been identified: ROCK1 and ROCK2. ROCK is composed of N-terminal catalytic, coiled-coil, and C-terminal PH (pleckstrin homology) domains. The C-terminus of ROCK negatively regulates its kinase activity. ROCK1 is cleaved by caspase-3 at a conserved DETD1113/G sequence resulting in loss of its C-terminal inhibitory domain. ROCK2 is directly cleaved by granzyme B (grB). Cleavage activates ROCK2 and leads to phosphorylation of myosin light chain (MLC) and inhibition of myosin phosphatase. This phosphorylation may account for the mechanism by which Rho regulates cytokinesis, cell motility, cell membrane blebbing during apoptosis, and smooth muscle contraction.
