Related Experiment Video

Updated: Jun 14, 2026

Transverse Aortic Constriction in Mice
08:25

Transverse Aortic Constriction in Mice

Published on: April 21, 2010

MAPK-activated protein kinase-2 in cardiac hypertrophy and cyclooxygenase-2 regulation in heart

John M Streicher1, Shuxun Ren, Harvey Herschman

  • 1Department of Anesthesiology, David Geffen School of Medicine, University of California, Los Angeles, CA 91301, USA.

Circulation Research
|March 27, 2010
PubMed
Abstract

Insights

p38 activation in heart causes lethal cardiomyopathy, but inactivating its downstream kinase, MAPK-activated protein kinase-2 (MK2), partially prevents this. MK2 plays a key role in p38-induced cardiac pathology.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Signal Transduction

Background:

  • p38 mitogen-activated protein kinase (MAPK) influences cardiac gene expression, contractility, and inflammation.
  • The role of p38 in cardiac hypertrophy is debated.
  • MAPK-activated protein kinase-2 (MK2) is a downstream kinase of p38, but its role in cardiac pathology is unknown.

Purpose of the Study:

  • To investigate the specific contribution of MK2 to p38-induced pathological cardiac remodeling.
  • To elucidate the downstream mechanisms by which p38 signaling affects the heart.

Main Methods:

  • Utilized a cardiomyocyte-specific, inducible transgenic mouse model.
  • Compared p38 activation effects in wild-type and MK2-null backgrounds.
  • Assessed cardiac function, hypertrophy, fibrosis, gene expression, and protein synthesis.

Main Results:

  • p38 activation in wild-type mice induced lethal cardiomyopathy with hypertrophy, fibrosis, and dysfunction.
  • MK2 inactivation partially rescued cardiomyocyte hypertrophy, improved contractility, and prevented lethality.
  • MK2 was crucial for COX-2 protein synthesis, independent of mRNA levels or protein stability.

Conclusions:

  • p38 signaling in adult cardiomyocytes contributes to pathological cardiac hypertrophy and remodeling.
  • MK2 is a significant downstream mediator of p38-induced cardiac pathology, particularly in protein synthesis regulation.

More Related Videos

Isolation, Culture, and Functional Characterization of Adult Mouse Cardiomyoctyes12:49

Isolation, Culture, and Functional Characterization of Adult Mouse Cardiomyoctyes

Published on: September 24, 2013

Related Concept Videos

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,...
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...
Cellular Adaptation II: Hypertrophy01:26

Cellular Adaptation II: Hypertrophy

Hypertrophy is the increase in the size of individual cells, resulting in the enlargement of a tissue or organ. Unlike hyperplasia, which involves an increase in cell number, hypertrophy is characterized by an increase in cell volume. This process often occurs in response to higher functional demand or hormonal stimulation, leading to the production of more structural proteins and organelles, thereby enhancing the cells' work capacity.There are two primary types of hypertrophy: physiological...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
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,...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include: