Related Experiment Video
Updated: Jul 26, 2026
09:58
RhoC GTPase Activation Assay
Published on: August 22, 2010
An essential role for Rac in Ras transformation
Nature
|March 30, 1995
Summary
The GTPase Rac1 protein is crucial for cell transformation, driving malignant characteristics. Oncogenic Ras utilizes Rac1 and MAP-kinase pathways, which cooperate to promote cell transformation.
Area of Science:
- Cell biology
- Molecular oncology
- Signal transduction
Background:
- The GTPase Rac1 regulates actin cytoskeleton reorganization.
- Growth factors and oncogenic Ras1 induce actin reorganization.
- Rac1 is implicated in cell transformation processes.
Purpose of the Study:
- To investigate the role of Rac1 in cell transformation.
- To determine if Rac1 is essential for Ras-induced transformation.
- To elucidate the cooperation between Rac1 and other signaling pathways in transformation.
Main Methods:
- Utilized NIH3T3 fibroblasts for focus-forming assays.
- Employed activated Val-12 Rac1 to induce transformation hallmarks.
- Used dominant-negative Asn-17 Rac1 to inhibit specific pathways.
- Investigated the effect of RafCAAX, a plasma membrane-targeted Raf kinase.
Main Results:
- Fibroblasts expressing activated Val-12 Rac1 exhibited malignant transformation characteristics.
- Dominant-negative Asn-17 Rac1 inhibited focus formation induced by oncogenic Ras.
- Dominant-negative Asn-17 Rac1 did not inhibit focus formation by RafCAAX.
- Activated Val-12 Rac1 synergized with RafCAAX in focus-formation assays.
Conclusions:
- Rac1 is essential for Ras-mediated cell transformation.
- Oncogenic Ras activates both Rac and MAP-kinase pathways.
- These pathways cooperate to drive malignant cell transformation.
Related Concept Videos
01:42Directionality of Nuclear Transport
Ras-related nuclear protein or Ran is a small G protein that cycles between its GTP and GDP bound states. Ran specific regulators, a Ran GTPase Activating Protein or RanGAP present in the cytosol and a Ran guanine nucleotide exchange factor or RanGEF present inside the nucleus regulate GTP/GDP exchange. A high concentration of GTP inside the cells, in addition to this asymmetric distribution of Ran-specific regulators, leads to a higher RanGTP concentration inside the nucleus. This...
02:38The Ras Gene
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Ras is a superfamily...
01:21Cell Polarization by Rho Proteins
Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...
01:24Small GTPases - Ras and Rho
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
01:07MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
02:38The Ras Gene
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Ras is a superfamily...