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. 2013 Dec 2;124(1):328–337. doi: 10.1172/JCI71471

Figure 6. ROCK targets responsible for cytoskeleton assembly.

Figure 6

Modulation of cytoskeleton assembly is required for the coordination of cell adhesion, polarization and migration. The active form of RhoA (RhoA-GTP) activates ROCK and interacts with the integrin intracellular signaling pathway. RhoA also modulates cytoskeleton reorganization via focal adhesion kinase (FAK) activation and front-rear polarity via phosphorylation of phosphatase and tensin homolog (PTEN). Phosphorylation of ROCK’s downstream effector MLC is required for the assembly of actomyosin complexes. ROCK downregulates the MLC phosphatase (MLCPase), resulting in an increase in phosphorylated MLC, cell contraction, actin organization, stress fiber formation, and focal adhesions, which confer contractility and migration properties to the cell. Phosphorylation of ROCK’s downstream effector ERM has a role in microvilli formation. Phosphorylated LIM domain kinase (LIM-K) phosphorylates and thus deactivates the actin-depolymerizing protein cofilin. Y-27632 blocks Rho-induced actomyosin activation. These data support a role for TTC7A in the downregulation of ROCK activity. Activation and inactivation are shown as arrowheads and blunted lines, respectively. MLCK, myosin light chain kinase; NHE1, Na+/H+ exchange protein.