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RhoD Inhibits RhoC-ROCK-Dependent Cell Contraction via PAK6.

Developmental cell | May 8, 2017

RhoA-mediated regulation of myosin-II activity in the actin cortex controls the ability of cells to contract and bleb during a variety of cellular processes, including cell migration and division. Cell contraction and blebbing also frequently occur as part of the cytopathic effect seen during many different viral infections. We now demonstrate that the vaccinia virus protein F11, which localizes to the plasma membrane, is required for ROCK-mediated cell contraction from 2 hr post infection. Curiously, F11-induced cell contraction is dependent on RhoC and not RhoA signaling to ROCK. Moreover, RhoC-driven cell contraction depends on the upstream inhibition of RhoD signaling by F11. This inhibition prevents RhoD from regulating its downstream effector Pak6, alleviating the suppression of RhoC by the kinase. Our observations with vaccinia have now demonstrated that RhoD recruits Pak6 to the plasma membrane to antagonize RhoC signaling during cell contraction and blebbing.

Pubmed ID: 28486133 RIS Download

Mesh terms: Actins | Cell Line, Tumor | Cell Movement | Humans | Signal Transduction | p21-Activated Kinases | rho GTP-Binding Proteins | rhoA GTP-Binding Protein | rhoC GTP-Binding Protein

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Associated grants

  • Agency: Wellcome Trust, Id:
  • Agency: Medical Research Council, Id:
  • Agency: Cancer Research UK, Id:

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