Caspase-3-mediated Cleavage of ROCK I Induces MLC Phosphorylation and Apoptotic Membrane Blebbing

Nat Cell Biol. 2001 Apr;3(4):346-52. doi: 10.1038/35070019.

Abstract

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 sequence and its carboxy-terminal inhibitory domain is removed, resulting in deregulated and constitutive kinase activity. ROCK proteins are known to regulate MLC-phosphorylation, and apoptotic cells exhibit a gradual increase in levels of phosphorylated MLC concomitant with ROCK I cleavage. This phosphorylation, as well as membrane blebbing, is abrogated by inhibition of caspases or ROCK proteins, but both processes are independent of Rho activity. We also show that expression of active truncated ROCK I induces cell blebbing. Thus, activation of ROCK I by caspase-3 seems to be responsible for bleb formation in apoptotic cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Binding Sites
  • Caspase 3
  • Caspases / metabolism*
  • Cell Membrane / pathology
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Jurkat Cells
  • Myosin Light Chains / metabolism*
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • U937 Cells
  • rho-Associated Kinases
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Intracellular Signaling Peptides and Proteins
  • Myosin Light Chains
  • Protein-Serine-Threonine Kinases
  • rho-Associated Kinases
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • rhoA GTP-Binding Protein