Target intelligence / Profile preview

Extracellular signal-regulated kinase (ERK)

Target
ERK
Molecular classification
Enzyme, Protein Kinase, Serine/threonine kinase, MAP Kinase, MAPK
01

Overview

Extracellular signal-regulated kinases (ERKs) are a family of serine/threonine protein kinases that play a central role in the mitogen-activated protein kinase (MAPK) signaling pathway. They are key intracellular signaling molecules involved in regulating diverse cellular processes, including proliferation, differentiation, survival, migration, and gene expression. Dysregulation of the Ras-Raf-MEK-ERK pathway is implicated in many cancers, and aberrant activity has been linked with chronic inflammation disorders. ERKs are activated by dual phosphorylation on threonine and tyrosine residues by MEK1/2, leading to dimerization, translocation to the nucleus, and phosphorylation of various transcription factors. They can also be activated by other mechanisms including Ca²⁺ influxes or G-protein-coupled receptor pathways.

Other names
MAPK3p44 MAPKERK1MAPK1p42 MAPKERK2
02

Mechanism of action

Inhibition of ERK phosphorylation and activation, or inhibition of upstream kinases in the MAPK pathway such as B-Raf or MEK.

03

Biological functions

Cell proliferationDifferentiationSurvivalApoptosis resistanceMigrationInvasionMetabolism regulationTranscriptional controlSignal transduction
04

Disease associations

CancerChronic inflammationArthritisOsteoporosis
05

Safety considerations

Resistance to inhibitorsOff-target effects of inhibitorsToxicityLimited clinical efficacy of some inhibitors
06

Interacting drugs

Inhibitors targeting mutant B-Raf(V600E)

1 more in the full profile.

07

Biomarkers

ERK phosphorylation statusMutations in Ras, B-Raf, or receptor tyrosine kinases (e.g. HER2)

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