Mitogen-activated protein kinase signaling cascade (MAPK signaling cascade)

The mitogen-activated protein kinase (MAPK) signaling cascade is a central intracellular pathway that communicates signals from surface receptors to the DNA in the cell nucleus. It typically operates through a three-tier kinase architecture consisting of a MAP3K (such as Raf), a MAP2K (such as MEK), and a MAPK (such as ERK) [NIH, 2022]. This pathway is essential for regulating fundamental cellular processes including growth, proliferation, and survival in response to mitogens and stress [UniProt, 2023]. Mutations that cause constitutive activation of the MAPK cascade, particularly in the Ras or BRAF proteins, are frequently observed in various cancers, most notably melanoma, colorectal cancer, and non-small cell lung cancer [Nature Reviews Cancer, 2020]. Therapeutic strategies focus on inhibiting specific components like BRAF or MEK to shut down the overactive signaling that drives tumor growth. While highly effective, these treatments often face challenges such as the development of secondary resistance and significant dermatological or cardiovascular side effects [PubMed, 2021].

Other names

MAPK pathwayRas-Raf-MEK-ERK pathwayERK signaling pathwayMitogen-activated protein kinase pathway

Inhibition of specific kinase nodes (primarily BRAF and MEK1/2) within the cascade to suppress downstream phosphorylation of ERK, thereby halting oncogenic signaling and cell cycle progression [StatPearls, 2023].