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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:

GTPases and their Regulation

GTPases and their Regulation

Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins,...

GTPases and their Regulation

GTPases and their Regulation

Activation and Inactivation of G Proteins

Activation and Inactivation of G Proteins

Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...

Rab Cascades

Rab Cascades

Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.

Rab Proteins

Rab Proteins

Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...

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Related Experiment Video

Updated: Apr 5, 2026

Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay

Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay

Published on: November 11, 2018

Drugging the Ral GTPase.

Chao Yan¹, David N M Jones, Dan Theodorescu

¹a Departments of Surgery (Urology) and Pharmacology ; University of Colorado ; Aurora , CO USA.

|August 18, 2015

Summary

This summary is machine-generated.

Small molecule inhibitors targeting RAL GTPases show promise in fighting lung cancer. These novel compounds, which block tumor growth and metastasis, offer new therapeutic strategies for cancer treatment.

Keywords:

GTPase Ral Ras allosteric metastasis personalized medicine precision medicine small molecule targeted therapy

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Comparing the Affinity of GTPase-binding Proteins using Competition Assays

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Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

Related Experiment Videos

Last Updated: Apr 5, 2026

Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay

Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay

Published on: November 11, 2018

Comparing the Affinity of GTPase-binding Proteins using Competition Assays

Comparing the Affinity of GTPase-binding Proteins using Competition Assays

Published on: October 8, 2015

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

Area of Science:

Oncology
Molecular Biology
Biochemistry

Background:

RAL GTPases are key regulators of cell growth and are implicated in various cancers.
Dysregulation of RAL GTPases contributes to tumor progression and metastasis.

Purpose of the Study:

To develop and characterize novel small molecule inhibitors of RAL GTPases.
To evaluate the antitumor activity of these inhibitors in human lung cancer models.

Main Methods:

Development of allosteric, non-competitive inhibitors targeting GDP-bound RAL.
In vitro testing of inhibitor efficacy against human lung cancer cell lines.

Main Results:

Successfully developed the first small molecule inhibitors of RAL with demonstrated antitumor activity.
Inhibitors bind to an allosteric site on GDP-bound RAL, blocking its function.

Conclusions:

RAL GTPase inhibitors represent a promising new therapeutic avenue for lung cancer.
These inhibitors may be effective in combination therapies targeting the RAS signaling pathway.
The findings provide a basis for targeting other GTPases.