Mitogen-activated protein kinase pathway kinases (MAPK pathway kinases)

The Mitogen-activated protein kinase (MAPK) pathway kinases constitute a fundamental signaling network that transmits extracellular signals from the cell surface to the nucleus to regulate essential cellular processes (StatPearls, 2023). This pathway typically operates through a three-tiered kinase cascade: a MAP kinase kinase kinase (MAP3K, such as RAF), which phosphorylates a MAP kinase kinase (MAP2K, such as MEK1/2), which in turn activates a MAP kinase (MAPK, such as ERK1/2) (UniProt, 2024). The Ras-Raf-MEK-ERK axis is the most prominent of these cascades and is frequently dysregulated in human cancers due to gain-of-function mutations in upstream components like KRAS or BRAF (NIH, 2024). Therapeutic targeting of these kinases has revolutionized the treatment of malignancies like metastatic melanoma, with inhibitors of BRAF and MEK being used to suppress oncogenic signaling (PubMed, PMID: 32810090). However, the clinical utility of these agents is often limited by the rapid emergence of acquired resistance and a range of class-specific toxicities, including dermatological reactions and cardiotoxicity (PubMed, PMID: 29441108).

Other names

MAPK cascadeRas-Raf-MEK-ERK pathwayMitogen-activated protein kinase signaling pathwayMAP kinase pathwayERK signaling cascade

Inhibition of specific kinase nodes within the signaling cascade (e.g., RAF, MEK, or ERK) to prevent downstream phosphorylation and subsequent activation of transcription factors involved in cell growth (NCBI, 2023).