FIG. 4.

RhoA signaling pathways. (A) Indirect inhibition of RhoA by Rac1-mediated ROS production. Cell adhesion and resulting Rac1 activation leads to ROS generation through Nox. ROS production inactivates LMW-PTP, resulting in increased phosphorylation of p190 Rho-GAP and, subsequently, its activation. Enhanced GAP activity results in decreased RhoA activity, which promotes cell spreading. (B) Inactivation of RhoA by NO leads to increased p21 expression. p21 expression inhibits smooth muscle cell proliferation. NO is thought to inactivate RhoA directly by S-nitrosation. (C) In addition to indirect regulation by RI, RhoA can be directly activated by ROS or RNS. ROS treatment of cells leads to enhanced nucleotide exchange and RhoA activation. RhoA activation enhances stress fiber formation. LMW-PTP, low-molecular-weight protein tyrosine phosphatase; MLC-p, phosphorylated myosin light-chain; Nox, NADPH oxidase; RNS, reactive nitrogen species; ROCK, Rho-associated protein kinase; ROS, reactive oxygen species; SMC, smooth muscle cells.