The MAPK/ERK pathway is a critical signaling cascade that regulates cell proliferation, differentiation, and survival.
The MAPK/ERK pathway (also known as the RAS-RAF-MEK-ERK pathway) is one of the most well-studied signaling cascades in cell biology. It transmits signals from cell surface receptors to the nucleus, regulating gene expression involved in cell proliferation, differentiation, and survival.
| Component | Function | Dysregulation in Disease |
|---|---|---|
| RAS (KRAS, NRAS, HRAS) | Small GTPase that activates RAF | Mutated in ~30% of all cancers |
| RAF (ARAF, BRAF, CRAF) | Serine/threonine kinase | BRAF V600E mutation in melanoma |
| MEK (MEK1, MEK2) | Dual-specificity kinase | Overactive in various cancers |
| ERK (ERK1, ERK2) | Proline-directed kinase | Hyperactivated in many tumors |
Upon growth factor binding to receptor tyrosine kinases (RTKs), RAS is activated through GDP-to-GTP exchange. Activated RAS recruits RAF to the membrane, which phosphorylates and activates MEK. MEK then phosphorylates ERK, which phosphorylates numerous cytoplasmic and nuclear targets.
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