Rho GTPase signaling pathway (Rho signaling)

Rho GTPase signaling is a central regulatory network involving small GTP-binding proteins that act as molecular switches to control diverse cellular processes, most notably the organization of the actin cytoskeleton (Haga & Ridley, 2016, Nature Reviews Molecular Cell Biology). The pathway is primarily driven by members of the Rho family, including RhoA, Rac1, and Cdc42, which transition between active GTP-bound and inactive GDP-bound states under the regulation of Guanine Nucleotide Exchange Factors (GEFs), GTPase-Activating Proteins (GAPs), and Guanine Nucleotide Dissociation Inhibitors (GDIs) (Cherfils & Zeghouf, 2013, Physiological Reviews). These proteins relay extracellular signals to downstream effectors like Rho-associated protein kinase (ROCK) to modulate cell shape, motility, adhesion, and proliferation (Riento & Ridley, 2003, Nature Reviews Molecular Cell Biology). In pathological contexts, aberrant Rho signaling is a hallmark of cancer metastasis, where it promotes cell invasion, and cardiovascular diseases, where it contributes to vascular smooth muscle contraction and hypertension (Sahai & Marshall, 2002, Nature Reviews Cancer; Shimokawa et al., 2016, Circulation Research). Pharmacological intervention typically targets the downstream kinases or the regulatory enzymes of the pathway, with ROCK inhibitors like fasudil and netarsudil being the most clinically advanced class of therapeutics (Feng et al., 2015, Journal of Medicinal Chemistry).

Other names

Rho family GTPase signalingRho-mediated signalingRho GTPase cascade

Inhibition of downstream effectors such as Rho-associated protein kinase (ROCK), blockade of guanine nucleotide exchange factor (GEF) interactions, or inhibition of post-translational prenylation required for membrane localization (Feng et al., 2015; Liao & Laufs, 2005).