Related Experiment Video

Updated: Jul 29, 2026

Assaying Protein Kinase Activity with Radiolabeled ATP
08:05

Assaying Protein Kinase Activity with Radiolabeled ATP

Published on: May 26, 2017

Phosphorylation of elk-1 by MEK/ERK pathway is necessary for c-fos gene activation during cardiac myocyte hypertrophy

G J Babu1, M J Lalli, M A Sussman

  • 1Laboratory of Molecular Cardiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Journal of Molecular and Cellular Cardiology
|July 30, 2000
PubMed

Insights

Signaling kinases like ERK are crucial for cardiac hypertrophy. This study shows that ERK phosphorylates Elk-1, a transcription factor, which activates early gene expression like c-fos during hypertrophy.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Gene Regulation

Background:

  • Cardiac hypertrophy involves altered myocardial gene expression.
  • Mechanisms driving these gene expression changes are not fully understood.
  • Investigating signaling pathways is key to understanding cardiac remodeling.

Purpose of the Study:

  • To determine if signaling kinases activated during cardiac hypertrophy directly regulate transcription factor activity.
  • To elucidate the role of these kinases in controlling gene expression during myocyte hypertrophy.
  • To focus on the transcriptional activation of the c-fos gene via the SRE/TCF pathway.

Main Methods:

  • Studied phenylephrine-induced myocyte hypertrophy model.
  • Investigated the binding of phosphorylated Elk-1 (a TCF) to the c-fos serum response element (SRE).
  • Utilized MEK/ERK kinase inhibitors to assess pathway involvement.

Main Results:

  • Phosphorylated Elk-1 binds to the c-fos SRE, with binding increasing upon phenylephrine stimulation.
  • Phenylephrine rapidly induces Elk-1 phosphorylation in the nucleus.
  • MEK/ERK kinase inhibitors blocked Elk-1-dependent transcriptional activation.

Conclusions:

  • Phosphorylation of Elk-1 by the MEK/ERK pathway is essential for early gene activation in phenylephrine-induced cardiac hypertrophy.
  • This pathway plays a critical role in the molecular response to hypertrophic stimuli.
  • Elucidates a key mechanism in the regulation of gene expression during cardiac hypertrophy.

More Related Videos

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes09:16

Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes

Published on: June 3, 2018

Related Concept Videos

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...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
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...
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...
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,...
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...