The MAPK (mitogen-activated protein kinase) cascades are conserved signalling pathways that convert extracellular signals into cellular responses such as proliferation, differentiation, stress responses and apoptosis.
The three main MAPK pathways
- ERK1/2 (Ras–Raf–MEK–ERK): the classic growth-factor pathway driving proliferation and differentiation. A growth factor activates a receptor tyrosine kinase → Ras → Raf (MAPKKK) → MEK1/2 (MAPKK) → ERK1/2 (MAPK), which phosphorylates transcription factors and other targets.
- JNK (c-Jun N-terminal kinase): a stress-activated pathway responding to cytokines, UV and osmotic stress; regulates apoptosis and inflammation.
- p38: also stress-activated; important in inflammation, cytokine production and the cell cycle.
The three-tier kinase module
All MAPK cascades share the same architecture: a MAPKKK phosphorylates a MAPKK, which phosphorylates the terminal MAPK. This relay amplifies the signal and provides points for regulation and crosstalk.
Why it matters
The Ras–Raf–MEK–ERK pathway is one of the most frequently mutated in cancer (e.g. RAS and BRAF mutations), and MEK/BRAF inhibitors are established targeted therapies. p38 and JNK are major targets in inflammation research.
Explore the pathway
- KEGG: MAPK signalling pathway
- Reactome — search “MAPK” for curated, interactive diagrams.
- Cell Signaling Technology pathways
Frequently asked questions
What does the MAPK pathway do?
It transmits extracellular signals (e.g. growth factors, stress) to the nucleus, controlling proliferation, differentiation, stress responses and apoptosis.
What are the three MAPK cascades?
ERK1/2 (growth/proliferation), JNK and p38 (both stress-activated).
Why is MAPK important in cancer?
The Ras–Raf–MEK–ERK arm is frequently mutated (RAS, BRAF), and inhibitors of BRAF and MEK are used clinically.
