Negative regulation of ERK and Elk by protein kinase B modulates c-Fos transcription

Related Experiment Video

Updated: Sep 28, 2026

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
10:28

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers

Published on: September 20, 2018

Ivana Galetic1, Sauveur-Michel Maira, Mirjana Andjelkovic

  • 1Friedrich Miescher Institute, P. O. Box 2543, CH-4002 Basel, Switzerland.

The Journal of Biological Chemistry
|December 7, 2002
PubMed

Insights

Protein kinase B (PKB) suppresses the MAPK pathway, reducing Elk1 activity and c-fos transcription. This PKB action promotes cell survival and may contribute to oncogenic transformation.

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Cancer research

Background:

  • Cross-talk between protein kinase B (PKB) and MAPK pathways is crucial for cellular regulation.
  • The Ras-Raf-MEK-ERK pathway and transcription factor Elk1 play roles in gene expression.
  • Immediate-early genes like c-fos are involved in cellular responses, including apoptosis and transformation.

Purpose of the Study:

  • To identify novel regulatory mechanisms in PKB and MAPK signaling pathway cross-talk.
  • To elucidate the role of PKB in regulating the Ras-Raf-MEK-ERK pathway and downstream targets.
  • To investigate the impact of PKB on immediate-early gene transcription and cell survival.

Main Methods:

  • Investigated the activity of ERK and Elk1 in response to PKB modulation.
  • Assessed protein levels of Elk1 and c-fos.
  • Analyzed serum response element (SRE)-dependent transcription.
  • Utilized glioblastoma cells with constitutively active PKB.

Main Results:

  • PKB down-regulates the Ras-Raf-MEK-ERK pathway by reducing ERK activity.
  • PKB leads to inactivation and reduced protein levels of the transcription factor Elk1.
  • Suppression of SRE-dependent transcription and decreased c-fos gene transcription were observed.
  • Constitutively active PKB reduced c-Fos protein levels in glioblastoma cells.

Conclusions:

  • PKB plays a significant role in suppressing immediate-early transcription via the MAPK pathway.
  • PKB's regulation of Elk1 and c-fos contributes to cell survival.
  • This novel mechanism may be involved in PKB-induced oncogenic transformation.

More Related Videos

Spatial and Temporal Analysis of Active ERK in the C. elegans Germline08:40

Spatial and Temporal Analysis of Active ERK in the C. elegans Germline

Published on: November 29, 2016

Assaying Protein Kinase Activity with Radiolabeled ATP08:05

Assaying Protein Kinase Activity with Radiolabeled ATP

Published on: May 26, 2017

Related Concept Videos

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...
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...