S-23

Overview

RhoA is a small signaling G protein, and is a member of the Rho family of GTPases. It is encoded by the RHOA gene in humans. RhoA is involved in many cellular processes, including the regulation of the actin cytoskeleton, cell migration, cell cycle progression, and gene expression.

Structure

RhoA is a small GTPase, which means it can bind and hydrolyze guanosine triphosphate (GTP). It has a molecular weight of approximately 21 kDa. Like other GTPases, RhoA cycles between an active GTP-bound state and an inactive GDP-bound state. The switch between these states is regulated by guanine nucleotide exchange factors (GEFs), which promote the exchange of GDP for GTP, and GTPase-activating proteins (GAPs), which enhance the intrinsic GTPase activity of RhoA, leading to the hydrolysis of GTP to GDP.

Function

RhoA plays a critical role in the regulation of the actin cytoskeleton. It is involved in the formation of stress fibers and focal adhesions, which are important for cell shape and motility. RhoA also regulates the formation of contractile actomyosin bundles, which are essential for cell contraction and cytokinesis.

In addition to its role in cytoskeletal dynamics, RhoA is involved in the regulation of cell cycle progression. It has been shown to influence the transition from the G1 phase to the S phase of the cell cycle. RhoA also plays a role in the regulation of gene expression by modulating the activity of transcription factors such as serum response factor (SRF).

Signaling Pathways

RhoA is activated by various extracellular signals, including growth factors, cytokines, and mechanical stress. Upon activation, RhoA interacts with a variety of downstream effectors, including Rho-associated protein kinase (ROCK), mammalian diaphanous-related formin (mDia), and LIM kinase. These effectors mediate the diverse cellular functions of RhoA.

Clinical Significance

Dysregulation of RhoA signaling has been implicated in various diseases, including cancer, cardiovascular diseases, and neurological disorders. In cancer, RhoA is often overexpressed or hyperactivated, leading to increased cell migration and invasion, which contributes to tumor metastasis. In cardiovascular diseases, RhoA signaling is involved in the regulation of vascular tone and blood pressure.

Research and Therapeutic Potential

Given its central role in many cellular processes, RhoA is a target of interest for therapeutic intervention. Inhibitors of RhoA and its downstream effectors, such as ROCK inhibitors, are being investigated for their potential to treat diseases such as cancer, hypertension, and glaucoma.

Also see

• Rho family of GTPases
• Actin cytoskeleton
• Cell migration
• Guanine nucleotide exchange factor
• GTPase-activating protein