Caspase-3-mediated cleavage of ROCK I induces MLC phosphorylation and apoptotic membrane blebbing

Increased phosphorylation of myosin light chain (MLC) is necessary for the dynamic membrane blebbing that is observed at the onset of apoptosis. Here we identify ROCK I, an effector of the small GTPase Rho, as a new substrate for caspases. ROCK I is cleaved by caspase-3 at a conserved DETD1113/G seq uence and its carboxy-terminal inhibitory domain is removed, resulting in d eregulated and constitutive kinase activity. ROCK proteins are known to reg ulate MLC-phosphorylation and apoptotic cells exhibit a gradual increase in levels of phosphorylated MLC concomitant with ROCK I cleavage. This phosph orylation, as well as membrane blebbing, is abrogated by inhibition of casp ases or ROCK proteins, but both processes are independent of Rho activity. We also show that expression of active truncated ROCK I induces cell blebbi ng. Thus, activation of ROCK I by caspase-3 seems to be responsible for ble b formation in apoptotic cells.