Target intelligence / Profile preview

Mitogen-activated protein kinase enzyme (MAPK) (MAPK)

Target
MAPK
Molecular classification
Enzyme (protein kinase: serine/threonine kinase), Signal transduction enzyme, Member of the CMGC kinase group (includes CDK, MAPK, GSK3, CLK)
01

Overview

Mitogen-activated protein kinase enzymes (MAPKs) are central serine/threonine protein kinases in eukaryotic cells that regulate the transduction of extracellular signals into cellular responses. The classical MAPKs (ERK, JNK, and p38 kinases) function as part of three-tiered phosphorylation cascades, modulating processes including growth, proliferation, differentiation, survival, apoptosis, immune response, and stress adaptation. These enzymes respond to diverse signals (growth factors, cytokines, stress stimuli) and are implicated in the pathogenesis of cancer, inflammatory diseases, and other disorders. MAPK pathway enzymes are therapeutic targets for multiple small-molecule inhibitors, especially in cancer therapy, although they present challenges including resistance and toxicity.

Other names
MAP kinasesMAPK enzymesMitogen-activated protein kinases (MAPK)ERK (Extracellular signal-regulated kinase family)JNK (c-Jun N-terminal kinases)p38 kinases
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Mechanism of action

Inhibition of phosphorylation activity (blocks kinase cascade) Disruption of downstream signaling (blocks cell proliferation, induces apoptosis) Interference with substrate binding and activation loop phosphorylation Modulation of gene expression via transcription factor regulation

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Biological functions

Signal transductionCell proliferationCell differentiationApoptosis (cell death)Cell survivalCell cycle regulationStress responseImmune responseMetabolism
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Disease associations

Cancer (critical role in development, progression, and resistance)InflammationNeurodegenerative diseaseCardiovascular diseaseInfectionOther: metabolic disorders, autoimmune diseases
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Safety considerations

Off-target effects (kinase inhibitors can affect other pathways)Toxicity (e.g., in vivo use limited by organ toxicity, adverse immune reactions)Resistance development (secondary mutations, pathway rewiring)Combination therapy challenges (synergistic toxicities)
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Interacting drugs

MEK inhibitors (e.g., CI-1040, PD98059, UO126)

4 more in the full profile.

07

Biomarkers

Phosphorylated MAPK (e.g., p-ERK, p-JNK, p-p38)Expression/activity of pathway components (MAPK1, MAPK3, MEK, ERK, JNK, p38)Downstream targets (e.g., matrix metalloproteinases, cyclin D1)Genetic mutations (e.g., BRAF V600E, KRAS, NRAS activating mutations)

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