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Related Concept Videos

Small GTPases - Ras and Rho01:24

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:
Activation and Inactivation of G Proteins01:22

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 affinity and are together...
The Ras Gene02:38

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...
Cell Polarization by Rho Proteins01:21

Cell 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,...
Rab Proteins01:14

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...
GPCR Desensitization01:12

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...

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Related Experiment Video

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Comparing the Affinity of GTPase-binding Proteins using Competition Assays
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Comparing the Affinity of GTPase-binding Proteins using Competition Assays

Published on: October 8, 2015

PKCα phosphorylation of RhoGDI2 at Ser31 disrupts interactions with Rac1 and decreases GDI activity.

E M Griner1, M E A Churchill, D L Brautigan

  • 1Department of Microbiology, Immunology and Cancer Biology, Center for Cell Signaling, University of Virginia, Charlottesville, VA, USA.

Oncogene
|April 4, 2012
PubMed
Summary

Protein kinase C (PKC) inactivates RhoGDI2, a cancer metastasis suppressor, by phosphorylating Ser31. This phosphorylation reduces RhoGDI2 binding to GTPases, potentially neutralizing its tumor-suppressing function in cancers with active PKC.

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Last Updated: May 23, 2026

Comparing the Affinity of GTPase-binding Proteins using Competition Assays
10:37

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Published on: October 8, 2015

RhoC GTPase Activation Assay
09:58

RhoC GTPase Activation Assay

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Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay
13:51

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

Published on: November 11, 2018

Area of Science:

  • Cellular Biology
  • Molecular Oncology
  • Signal Transduction

Background:

  • Rho family GTPases are crucial for cellular functions, and their dysregulation is linked to cancer.
  • Guanine nucleotide dissociation inhibitors (GDIs) regulate GTPase activity by sequestering them in the cytosol.
  • RhoGDI2 functions as a metastasis suppressor, but its regulatory mechanisms are poorly understood.

Purpose of the Study:

  • To elucidate the regulatory mechanism of RhoGDI2 activity.
  • To identify the specific kinase responsible for RhoGDI2 modification.
  • To investigate the functional consequences of RhoGDI2 regulation in cancer.

Main Methods:

  • Stimulation of cells with phorbol 12-myristate 13-acetate (PMA) to induce RhoGDI2 phosphorylation.
  • Pharmacological inhibition and siRNA-mediated knockdown of protein kinase C (PKC) isoforms.
  • Analysis of RhoGDI2 binding to Rac1 using wild-type and phospho-mimetic mutants (S31E-RhoGDI2).
  • Assessment of activated Rac1 levels and membrane localization.

Main Results:

  • RhoGDI2 undergoes rapid phosphorylation at Ser31 upon PMA stimulation.
  • Conventional type PKCα was identified as the kinase responsible for Ser31 phosphorylation.
  • Phospho-mimetic S31E-RhoGDI2 showed reduced binding to Rac1.
  • S31E-RhoGDI2 failed to decrease activated Rac1 levels or its membrane association.

Conclusions:

  • PKC-mediated phosphorylation of RhoGDI2 at Ser31 represents a novel mechanism for its inactivation.
  • This regulatory pathway reduces RhoGDI2's ability to bind and inhibit GTPases like Rac1.
  • This mechanism may contribute to tumor progression by neutralizing RhoGDI2's metastasis-suppressing function in cancers expressing active PKCα.