OBJECTIVE Estradiol (E2) mediates numerous beneficial effects assigned to estrogens, but whereas mechanisms have been described at the endothelial level, direct effects on vascular smooth muscle cells (VSMC) are poorly documented. As evidence accumulates regarding the role of RhoA in vascular pathophysiology and the benefit of RhoA-Rho associated protein kinase (Rock) pathway inhibition, we ana...

In many organisms, the small guanosine triphosphatase RhoA controls assembly and contraction of the actomyosin ring during cytokinesis by activating different effectors. Although the role of some RhoA effectors like formins and Rho kinase is reasonably understood, the functions of another putative effector, Citron kinase (CIT-K), are still debated. In this paper, we show that, contrary to previ...

Rough topography enhances the activation of Wnt canonical signaling in vitro, and this mediates its effects on cell differentiation. However, the molecular mechanisms underlying topography-dependent control of Wnt signaling are still poorly understood. As the small GTPase RhoA controls cytoskeletal reorganization and actomyosin-induced tensional forces, we hypothesized that RhoA could affect th...

Brief treatment with transforming growth factor (TGF)-beta1 stimulated the migration of macrophages, whereas long-term exposure decreased their migration. Cell migration stimulated by TGF-beta1 was markedly inhibited by 10 mug/mL Tat-C3 exoenzyme. TGF-beta1 increased mRNA and protein levels of macrophage inflammatory protein (MIP)-1alpha in the initial period, and these effects also were inhibi...

To determine the molecular mechanisms of aggressive prostate cancer behavior, we studied RhoGTPases in high and low invasive variants of PC-3 prostate cancer cells. Prior studies with these cells revealed that elevated nuclear factor B (NFB) expression and activity were necessary for the highly invasive phenotype. In the current study, increased RhoA expression was found in the PC-3 highly inva...

The low molecular weight GTP-binding protein RhoA regulates many cellular events, including cell migration, organization of the cytoskeleton, cell adhesion, progress through the cell cycle and gene expression. Physical forces influence these cellular processes in part by regulating RhoA activity through mechanotransduction of cell adhesion molecules (e.g. integrins, cadherins, Ig superfamily mo...

RhoA and Rac1 are small GTPases primarily involved in cytoskeletal remodeling. Many biochemical studies have suggested that they are also key organizers of cell-substrate adhesion. Recently, fluorescence resonance energy transfer (FRET)-based indicators have been developed to visualize RhoA and Rac1 activity in living cells [Yoshizaki et al., J. Cell Biol. 162, 223 (2003); Pertz et al., Nature ...

e already knew the players—MgcRacGAP, Aurora B, and RhoA—and that knocking out any one of them caused failure of cytokinesis; but it wasn’t clear how they were connected. Now, it appears that Aurora B phosphorylates the GAP domain of MgcRacGAP, allowing it to turn its GAP activity toward RhoA, according to data from Yukinori Minoshima, Toshiyuki Kawashima, Toshio Kitamura (University of Tokyo, ...

Bordetella dermonecrotic toxin (DNT) catalyzes the transglutamination of glutamine-63/61 of Rho GTPases, thereby constitutively activating Rho proteins. Here we identified second substrates for transglutamination of RhoA by DNT. The enzymatically active fragment of DNT (residues 1136 to 1451, DeltaDNT) induced the incorporation of L-[(14)C]lysine in RhoA in a concentration-dependent manner. Als...

Determining the cellular level of activated form of RhoGTPases is of key importance to understand their regulatory functions in cell physiopathology. We previously reported scFvC1, that selectively bind to the GTP-bound form of RhoA, RhoB and RhoC. In this present study we generate, by molecular evolution, a new phage library to isolate scFvs displaying high affinity and selectivity to RhoA and...