Extracellular signal-regulated kinase–mitogen-activated protein kinase signaling pathway (ERK-MAPK signaling pathway)

The **extracellular signal-regulated kinase–mitogen-activated protein kinase (ERK-MAPK) signaling pathway** is a central cellular signaling cascade that conveys information from cell surface receptors (such as receptor tyrosine kinases and G protein-coupled receptors) to the nucleus, regulating gene expression and orchestrating a broad spectrum of cellular processes, including proliferation, differentiation, survival, apoptosis, and neuronal plasticity. The canonical pathway consists of the sequential activation of Ras, Raf (MAP3K), MEK (MAP2K), and ERK (MAPK), ultimately influencing cell fate through phosphorylation of various cytoplasmic and nuclear substrates. Dysregulation, mutation, or constitutive activation of this pathway is implicated in diverse diseases, particularly cancer, where it plays a pivotal role in tumorigenesis, progression, and resistance to therapy. Pharmacological inhibitors targeting components of the ERK-MAPK pathway have been developed and approved, especially for cancers harboring activating mutations in RAS or BRAF, although resistance and toxicity present ongoing therapeutic challenges[1][4][5][7][8]. **Note:** This entry is marked as "is_incorrect: true" because the **ERK-MAPK signaling pathway is a pathway, not a discrete molecular target (such as a single protein/receptor/enzyme)**. In drug discovery and pharmacology, targets are typically specific molecules rather than entire pathways, although drugs are designed to inhibit or modulate one or more components within the pathway (e.g., MEK, ERK, BRAF). For structured databases and most target ontology systems, it is more accurate to use the names and characteristics of the specific proteins (e.g., "Mitogen-activated protein kinase 1 (ERK2)" or "Mitogen-activated protein kinase kinase 1 (MEK1)") rather than referring to the pathway as a whole[2][5][7].

Other names

ERK/MAPK pathwayMAPK/ERK pathwayRas-Raf-MEK-ERK pathwayRas/MAPK pathway

Inhibition of kinase activity (blocking MEK, ERK, or upstream BRAF); Disruption of signal transduction (interrupting pathway at various nodes); Decreasing cell proliferation and inducing apoptosis in cancer [5][8]