RHOA Human
Description
Introduction
RHOA Human (Ras homolog gene family member A) is a small GTPase protein critical for regulating cytoskeletal dynamics, cell migration, and transcriptional control. Encoded by the RHOA gene on chromosome 3, this protein belongs to the Rho family of GTPases, which act as molecular switches in signal transduction pathways. Its dysregulation is implicated in various cancers and vascular disorders, making it a focal point in biomedical research .
Gene and Protein Structure
Biochemical Properties
| Parameter | Value | Source |
|---|---|---|
| Molecular Weight | ~27 kDa (with His-tag) | |
| Purity | >85% (SDS-PAGE) | |
| Applications | GTPase assays, binding studies | |
| Tag | N-terminal His-tag |
Cytoskeletal Regulation
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Actin stress fibers: Activates DIAPH1 (a formin) to promote actin polymerization .
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Contractility: ROCK kinases phosphorylate myosin light chain (MLC) and inhibit cofilin, enhancing cell migration .
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Cell polarity: Coordinates microtubule organization and focal adhesion dynamics .
Transcriptional Control
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c-Fos promoter: Modulates serum-, LPA-, and AIF4-induced signaling .
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Sox9 expression: Regulates transcriptional activity via actin-dependent mechanisms .
Cell Cycle and Development
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Gastrulation: Essential for mesoderm formation and stem cell differentiation .
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Angiogenesis: Overexpression of active RhoA inhibits endothelial cell proliferation and tube formation, reducing VEGFR-2 and NOS3 expression .
Cancer-Associated Roles
Key Findings:
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HCC: High RHOA levels correlate with diagnostic sensitivity (92.5%) and specificity (90.0%) .
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Gastric Cancer: Mutations (e.g., p.Tyr42Cys) disrupt RhoA function, enabling anoikis resistance and diffuse growth .
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Therapeutic Targeting: ROCK inhibitors (Y-27632) enhance angiogenesis in vitro, suggesting RhoA-independent pathways .
Vascular and Neurological Disorders
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Endothelial Dysfunction: Active RhoA reduces nitric oxide synthase (NOS3) activity, impairing vascular repair .
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Neurological Injury: RhoA-ROCK pathway mediates growth cone collapse, limiting axonal regeneration .
Tissue-Specific Expression
| Tissue | Expression Level | References |
|---|---|---|
| Liver | High | |
| Gastric Tissue | High (diffuse cancer) | |
| Endothelial Cells | Variable (context-dependent) | |
| Adipose Tissue | Moderate |
Mutation-Driven Pathways
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Biochemical Impact: RHOA mutations (e.g., A161P/V) alter nucleotide binding kinetics, increasing k off rates and reducing effector interactions .
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Therapeutic Resistance: Dominant-negative RhoA (T19N) enhances VEGF-induced angiogenic sprouting, highlighting RhoA’s role in suppressing vascular repair .
Diagnostic and Prognostic Markers
Product Specs
Product Science Overview
The Ras Homolog Gene Family Member A (RhoA) is a protein encoded by the RHOA gene. It belongs to the Rho family of small GTPases, which are known to act as molecular switches in various signal transduction pathways. These proteins play a crucial role in the regulation of the actin cytoskeleton, influencing cell shape, attachment, and motility .
RhoA cycles between an inactive GDP-bound state and an active GTP-bound state. In its active form, RhoA interacts with a variety of effector proteins to regulate cellular responses such as cytoskeletal dynamics, cell migration, and cell cycle progression . It is involved in a signal transduction pathway that links plasma membrane receptors to the assembly of focal adhesions and actin stress fibers .
RhoA is essential for several cellular processes:
- Cytoskeleton Organization: RhoA is primarily associated with the organization of the cytoskeleton. It regulates the formation of actin stress fibers and focal adhesions, which are critical for maintaining cell shape and enabling cell movement .
- Cell Cycle and Cytokinesis: RhoA plays a vital role in cell cycle progression and cytokinesis. It is involved in the formation of the myosin contractile ring during cell division, which is necessary for the successful completion of cytokinesis .
- Cell Migration and Adhesion: RhoA regulates cell migration by controlling the dynamics of the actin cytoskeleton. It is also required for the formation of apical junctions in keratinocyte cell-cell adhesion .
Overexpression of RhoA has been associated with tumor cell proliferation and metastasis. It is implicated in various cancers due to its role in promoting cell cycle progression and migration . Additionally, RhoA has been studied in the context of cardiac pathophysiology, where it has been shown to play a role in cardiac remodeling and cardiomyopathies .
Human recombinant RhoA is a form of the protein that is produced through recombinant DNA technology. This involves inserting the RHOA gene into an expression system, such as bacteria or yeast, to produce the protein in large quantities. Recombinant RhoA is used in research to study its function and role in various cellular processes and diseases.
