Related Experiment Video

Updated: Jul 4, 2026

RhoC GTPase Activation Assay
09:58

RhoC GTPase Activation Assay

Published on: August 22, 2010

ERK5 promotes Src-induced podosome formation by limiting Rho activation

Mark Schramp1, Olivia Ying, Tai Young Kim

  • 1Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720, USA.

The Journal of Cell Biology
|June 25, 2008
PubMed

Insights

Extracellular signal-regulated kinase 5 (ERK5) promotes Src-induced podosome formation by regulating Rho GTPase signaling. ERK5 limits Rho activation by inducing RhoGAP7, which is crucial for cell invasion.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Src activity is linked to tumorigenesis and the formation of invasive podosomes.
  • Podosome formation involves Rho GTPases and actin cytoskeleton reorganization.
  • Src signaling influences gene expression via mitogen-activated protein kinase (MAPK) pathways.

Purpose of the Study:

  • To investigate the role of MAPK signaling, specifically ERK5, in regulating podosome formation.
  • To understand the mechanism by which ERK5 influences Src-induced cell invasion.

Main Methods:

  • Utilized Src-transformed fibroblasts and ERK5-deficient cells.
  • Assessed RhoA activation, Rho-kinase inhibition (Y27632), and podosome formation.
  • Investigated the role of transcription factor myocyte enhancing factor 2C and RhoGAP7/DLC-1 expression.

Main Results:

  • ERK5 is constitutively activated in Src-transformed cells.
  • ERK5 deficiency in v-Src expressing cells resulted in increased RhoA activation, cellular retraction, and impaired podosome formation.
  • Rho-kinase inhibition restored cellular extension and podosome formation in ERK5-deficient cells.
  • ERK5 induced RhoGAP7 expression via myocyte enhancing factor 2C, and RhoGAP7 restored podosome formation in ERK5-deficient cells.

Conclusions:

  • ERK5 is essential for Src-induced podosome formation and cell invasion.
  • ERK5 promotes podosome formation by upregulating RhoGAP7, which suppresses RhoA activation.
  • This pathway highlights a novel mechanism linking MAPK signaling to cytoskeletal dynamics and cancer progression.

More Related Videos

Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation08:00

Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation

Published on: October 4, 2024

Affinity Precipitation of Active Rho-GEFs Using a GST-tagged Mutant Rho Protein (GST-RhoA(G17A)) from Epithelial Cell Lysates11:28

Affinity Precipitation of Active Rho-GEFs Using a GST-tagged Mutant Rho Protein (GST-RhoA(G17A)) from Epithelial Cell Lysates

Published on: March 31, 2012

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:
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,...
MAPK Signaling Cascades01:07

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 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...
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...
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...