RHOA

RhoA is a small GTPase of the Rho family, part of the Ras superfamily of hydrolase enzymes involved in signal transduction. It acts as a molecular switch cycling between an active GTP-bound form and an inactive GDP-bound form. In its active state, RhoA regulates assembly of actin filaments, formation of stress fibers, and focal adhesions, processes that control cell shape, polarity, and directional migration. RhoA also influences contractility and cytokinesis.

Activation and regulation: RhoA activity is controlled by three classes of regulators. Guanine nucleotide exchange factors (GEFs) promote GDP–GTP exchange to activate RhoA. GTPase-activating proteins (GAPs) accelerate intrinsic GTP hydrolysis to return RhoA to the inactive GDP-bound state. Guanine nucleotide dissociation inhibitors (GDIs) can sequester RhoA in the cytosol and modulate its localization. Post-translational modification by prenylation (geranylgeranylation) at the C-terminus enables membrane association, a prerequisite for efficient signaling.

Downstream effectors and outcomes: Once active, RhoA engages effectors such as Rho-associated kinase (ROCK1/ROCK2), which phosphorylate myosin light chain and promote contractility, and formins such as mDia1/2, which promote actin polymerization. Through these pathways, RhoA contributes to stress fibers, focal adhesions, cell migration, and cytokinesis, as well as gene expression and morphogenesis in development.

Clinical relevance: Abnormal RhoA signaling is linked to pathological states including cancer cell invasion and metastasis, fibrosis, and cardiovascular diseases. Because of its central role in cytoskeletal dynamics, RhoA and its effectors are targets of therapeutic research, with ROCK inhibitors among the most studied approaches.

Gene and family: The RHOA gene encodes the RhoA protein in humans and is one of several highly related Rho GTPases. It is broadly expressed and conserved across vertebrates.