RAS-RAF-MEK-ERK signaling pathway (MAPK pathway)

The **RAS-RAF-MEK-ERK signaling pathway** (commonly known as the MAPK/ERK pathway or simply the MAPK pathway) is one of the most critical intracellular signaling cascades, regulating core cellular processes such as proliferation, cell cycle progression, differentiation, survival, metabolism, and apoptosis. This highly conserved kinase cascade is activated by diverse extracellular signals, typically starting from ligand binding to receptor tyrosine kinases (e.g., EGFR) on the cell surface, which subsequently activate RAS GTPases. Activated RAS proteins recruit and activate RAF serine/threonine kinases, which then phosphorylate and activate MEK, leading to the activation of ERK (extracellular signal-regulated kinase). Activated ERK translocates to the nucleus and regulates transcription factors (such as c-MYC and FOXO3A), thereby modulating gene expression and cellular phenotypes. Dysregulation or activating mutations in this pathway are among the most prominent drivers in human cancers and are implicated in a spectrum of developmental and neurodegenerative disorders. As a "signal transduction" pathway rather than a discrete molecule (receptor/protein), the RAS-RAF-MEK-ERK cascade itself is not a single molecular target but a cluster of highly inter-connected protein targets. It is the target for numerous FDA-approved drugs (often specific for BRAF, MEK, or mutant KRAS), reflecting its centrality in biomedical research and therapeutics[1][2][3][4][5][6][7][8]. **Important note regarding "is_incorrect":** This entry does not refer to a single molecule or canonical "target" in the traditional sense (like a receptor or enzyme) but rather a **multi-protein signaling pathway**. For structured databases, it is generally preferable to describe and catalog the discrete protein components (e.g., KRAS, BRAF, MEK1, ERK1/2) as individual targets with unique identifiers. Referring to the entire "RAS/RAF/MAPK signaling pathway" as a target is therefore considered overly broad or non-specific and would be marked as "is_incorrect: true" for target curation purposes[4][5].

Other names

MAPK/ERK pathwayRas-Raf-MEK-ERK pathwayMitogen-activated protein kinase pathwayRAS-MAPK pathway

• Inhibition of RAF kinase activity • Inhibition of MEK kinase activity • Inhibition of mutant KRAS activity • Downregulation of ERK phosphorylation • Suppression of downstream transcriptional activation