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The Ras Gene

The 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...

Small GTPases - Ras and Rho

Small 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:

MAPK Signaling Cascades

MAPK 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...

The Ras Gene

The 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...

Regulation of Nuclear Protein Sorting

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...

Abnormal Proliferation

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...

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Related Experiment Video

Updated: Jun 11, 2026

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans

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Nucleophosmin and nucleolin regulate K-Ras signaling.

Kerry L Inder, Michelle M Hill, John F Hancock

Communicative & Integrative Biology

|June 30, 2010

Summary

Nucleophosmin (NPM) and nucleolin regulate K-Ras at the plasma membrane, enhancing signaling through the MAPK pathway. These proteins stabilize K-Ras and increase its nanoclustering, impacting cell communication.

Area of Science:

Cell Biology
Molecular Biology
Signal Transduction

Background:

Ras proteins, including K-Ras, form transient nanoclusters on the plasma membrane, crucial for MAPK pathway signaling.
Nucleophosmin (NPM) and nucleolin are primarily nucleolar proteins with known extra-nuclear roles.

Purpose of the Study:

To identify novel regulators of K-Ras plasma membrane interactions and their influence on MAPK signaling.
To investigate the role of NPM and nucleolin in K-Ras localization, clustering, and signaling.

Main Methods:

Proteomic screening to identify K-Ras interacting proteins.
Cellular localization studies to determine NPM and nucleolin presence at the plasma membrane.
Biochemical assays to assess K-Ras-NPM/nucleolin interactions and K-Ras membrane stability.

Keywords:

ERK activation K-Ras NPM nucleolin plasma membrane nanoclusters

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Analysis of K-Ras nanoclustering and MAPK pathway activation.

Main Results:

NPM and nucleolin were identified as novel regulators of K-Ras plasma membrane interactions.
A subset of NPM and nucleolin localizes to the plasma membrane inner leaflet and interacts with K-Ras, but not H-Ras.
This interaction is independent of K-Ras activation state and stabilizes K-Ras at the membrane.
NPM expression increases K-Ras nanoclustering, leading to enhanced MAPK pathway signaling.

Conclusions:

NPM and nucleolin represent a new class of K-Ras regulators.
These proteins modulate MAPK pathway signal transduction by influencing K-Ras membrane dynamics and clustering.