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Updated: Aug 9, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
Published on: July 17, 2019
p21ras: an oncoprotein functioning in growth factor-induced signal transduction
1Laboratory for Physiological Chemistry, Universiteit Utrecht, The Netherlands.
Abstract:
p21ras is a small GTPase that functions as a molecular switch in intracellular signal transduction pathways activated by a large variety of growth factors. In 50% of colorectal tumours, one of the genes for p21ras is mutated resulting in a constitutive active protein. Recently, progress has been made in the elucidation of the signalling pathways in which p21ras is involved. After a ligand binds to growth factor receptors, in particular receptor tyrosine kinases, a guanine nucleotide exchange factor is activated, which results in p21ras in the GTP-bound form. This GTP-bound form of p21ras interacts with the protein kinase raf1 and induces the activation of a kinase cascade, resulting in various cellular responses. This kinase cascade is part of an integrated network of both positive and negative signalling events.
Insights
Mutated p21ras (RAS oncogene family) proteins are constitutively active in 50% of colorectal tumors, driving aberrant cell signaling. Understanding these pathways is crucial for cancer research.
Area of Science:
- Molecular Biology
- Cellular Signaling
- Oncology
Background:
- p21ras (RAS oncogene family) is a GTPase acting as a molecular switch in signal transduction.
- Growth factors activate p21ras, which is frequently mutated in colorectal tumors, leading to constitutive activity.
Purpose of the Study:
- To elucidate the signaling pathways involving p21ras.
- To understand the role of mutated p21ras in colorectal tumorigenesis.
Main Methods:
- Analysis of intracellular signal transduction pathways.
- Investigating the interaction of p21ras with downstream effectors like raf1.
- Studying kinase cascade activation.
Main Results:
- Ligand binding to growth factor receptors activates guanine nucleotide exchange factors, leading to GTP-bound p21ras.
- GTP-bound p21ras activates raf1, initiating a kinase cascade.
- This cascade mediates cellular responses and is part of a complex signaling network.
Conclusions:
- Mutated p21ras plays a significant role in colorectal cancer by maintaining constitutive signaling.
- The p21ras-raf1 pathway is a key component of integrated cellular signaling networks.
- Further research into these pathways may reveal therapeutic targets for colorectal cancer.
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