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MAPK Signaling Pathway: Regulation, Functions, Disease Implications and Biomarker Analysis

What is the MAPK signaling pathway?

The MAPK signaling pathway (Mitogen-Activated Protein Kinase pathway) is a fundamental signal transduction cascade that converts extracellular stimuli, such as growth factors, cytokines, stress signals, and environmental cues, into specific cellular responses, including cell proliferation, differentiation, inflammation, stress adaptation, and apoptosis.

MAPK signaling acts as a central regulatory hub in normal physiology and disease. Dysregulation of this pathway is strongly associated with cancer, immune disorders, cardiovascular diseases, and neurodegenerative conditions, making it one of the most intensively studied signaling pathways in biomedical research.

MAP Kinase (MAPK) signaling pathway analysis with AnyGenes array.

MAPK pathway activity can be efficiently assessed by measuring gene expression of key pathway regulators, downstream targets, and branch-specific gene signatures.

MAPK signaling pathway biomarker list
View the genes included in our MAPK-related qPCR arrays.

Three major transduction pathways of the MAPK-signaling pathway.
Three major transduction pathways of the MAPK-signaling pathway. When chemical molecules of natural products enter the cell membrane, they interact with key target proteins of the MAPK-signaling pathway. These in turn activate the cascade response of the MAPK-signaling pathway, thereby regulating apoptosis in cancer cells.

Key takeaways – MAPK signaling pathway

  • Core pathway translating extracellular signals into gene expression programs
  • Organized as a three-tier kinase cascade (MAPKKK → MAPKK → MAPK)
  • Three major branches: ERK, JNK, and p38
  • Central role in cancer, inflammation, stress responses, and apoptosis
  • Highly suitable for targeted gene expression and biomarker analysis

Structure of the MAPK signaling cascade

MAPK signaling pathways are composed of three sequentially activated kinase tiers, ensuring signal amplification, specificity, and tight regulation.

MAP Kinase Kinase Kinases (MAPKKKs)

The upstream tier includes kinases such as RAF, activated by:

  • Growth factor receptors
  • Small GTPases (e.g. RAS)
  • Stress and inflammatory signals
  • Activated MAPKKKs phosphorylate and activate MAPKKs.

MAP Kinase Kinases (MAPKKs)

This intermediate tier includes kinases such as MEK1/2, which:

  • Integrate signals from MAPKKKs
  • Phosphorylate and activate MAPKs on conserved motifs

Mitogen-Activated Protein Kinases (MAPKs)

The terminal tier executes cellular responses by phosphorylating cytoplasmic and nuclear substrates, including transcription factors.

The three major MAPK branches are:

  • ERK (Extracellular signal-Regulated Kinase)
  • JNK (c-Jun N-terminal Kinase)
  • p38 MAPK

Major MAPK signaling pathways

ERK pathway

  • Primarily activated by growth factors and mitogens
  • Promotes cell proliferation, differentiation, and survival
  • Frequently dysregulated in cancer via RAS–RAF–MEK–ERK activation

JNK pathway

  • Activated by cellular stress, inflammatory cytokines, and DNA damage
  • Regulates apoptosis, immune responses, and stress adaptation
  • Plays a dual role in tumor suppression and tumor progression

p38 MAPK pathway

  • Strongly induced by environmental stress and inflammation
  • Controls cytokine production, cell cycle arrest, and apoptosis
  • Implicated in inflammatory and autoimmune diseases

Biological functions of MAP Kinase pathway

MAPK pathways regulate a wide range of essential biological processes:

  • Cell proliferation and differentiation: Especially mediated by ERK signaling through transcriptional regulation.
  • Apoptosis and survival: Balanced regulation via JNK and p38 signaling.
  • Inflammation and immune responses: Controls cytokine expression and immune cell activation.
  • Stress responses: Enables adaptation to oxidative stress, UV radiation, and DNA damage.
  • Signal amplification and specificity: Scaffold proteins organize pathway components to maintain fidelity and limit cross-talk.

Regulation of signaling activity

MAPK signaling is tightly controlled through:

  • Reversible phosphorylation and dephosphorylation
  • MAPK phosphatases (MKPs) that terminate signaling
  • Scaffold proteins that spatially organize pathway components

This multilayer regulation ensures precise signal duration and intensity, which is critical for normal cellular function.

MAP Kinase signaling pathway dysregulation and disease

  • Cancer

Constitutive activation of MAPK signaling—often through mutations in RAS, BRAF, or MEK—drives uncontrolled cell proliferation, survival, and therapy resistance.

MAPK signaling is a major therapeutic target in melanoma, lung cancer, colorectal cancer, and other malignancies.

  • Inflammatory and immune diseases

Aberrant JNK and p38 signaling contributes to:

  • Chronic inflammation
  • Autoimmune diseases
  • Dysregulated cytokine production
  • Cardiovascular and neurodegenerative diseases

MAPK pathway dysregulation is involved in:

  • Cardiac hypertrophy
  • Ischemic injury
  • Neuronal stress responses and degeneration

Why study the MAPK signaling pathway with AnyGenes?

At AnyGenes®, we provide high-performance qPCR arrays and customizable SignArrays® specifically designed for MAPK signaling pathway analysis and biomarker discovery.

Our solutions enable researchers to:

  • Quantify ERK-, JNK-, and p38-specific gene signatures
  • Analyze upstream regulators and downstream transcriptional targets
  • Investigate pathway cross-talk with PI3K/AKT, mTOR, and NF-κB
  • Generate robust, reproducible, and publication-ready gene expression data

MAPK signaling pathway biomarker analysis with AnyGenes®

What can be analyzed?

  • Core MAPK regulators and kinases
  • Downstream transcription factors
  • Stress- and inflammation-related genes
  • Disease-associated MAPK biomarkers

Available solutions

  • MAPK pathway–focused qPCR array solutions
  • Fully customizable SignArrays®
  • Expert guidance for experimental design and data interpretation

Customize your own signaling pathways (SignArrays®) with the factors of your choice!
Simply download and complete our Personalized SignArrays® information file and send it at [email protected] to initiate your project.

Frequently asked questions

MAPK signaling translates extracellular signals into cellular responses such as growth, stress adaptation, inflammation, and apoptosis.

The three major MAPK pathways are ERK, JNK, and p38.

Constitutive activation of the RAS–RAF–MEK–ERK cascade promotes uncontrolled proliferation and tumor progression.

Typical genes include RAF, MEK, ERK, JNK, p38, transcription factors, and stress-response genes.

Through targeted qPCR arrays or customized SignArrays® optimized for MAPK pathway biomarker analysis.

  1. Shi A, et al. Natural products targeting the MAPK-signaling pathway in cancer: overview. J Cancer Res Clin Oncol. (2024)9;150(1):6.
  2. Bahar ME, Kim HJ, Kim DR. Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies. Signal Transduct Target Ther. (2023)18;8(1):455.
  3. Yue J, López JM. Understanding MAPK Signaling Pathways in Apoptosis. Int J Mol Sci. (2020)28;21(7):2346.

MAP Kinase signaling pathway biomarker list

You can check the biomarker list included in this pathway, see below:

Species : Homo sapiens (human)

Human Signaling Pathways

Signaling PathwaysProduct refInformations

MAP Kinase (MAPK) Signaling Pathway

MAPK1H1

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Species : Mus musculus (mouse)

Mouse Signaling Pathways

Signaling PathwaysProduct refInformations

MAP Kinase (MAPK) Signaling Pathway

MAPK1M1

List infos


Species : Rattus norvegicus (rat)

Rat Signaling Pathways

Signaling PathwaysProduct refInformations

MAP Kinase (MAPK) Signaling Pathway

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List In progress...


Species : Sus Scrofa (Pig)

Pig Signaling Pathways

Signaling PathwaysProduct refInformations

MAP Kinase (MAPK) Signaling Pathway

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List In progress...


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