Mitogen-activated protein kinase pathway signaling complexes (MAPK pathway)

The Mitogen-activated protein kinase (MAPK) pathway signaling complexes are critical mediators of cellular responses to extracellular signals, including growth factors, cytokines, and environmental stress [1]. These complexes typically consist of a three-tier kinase cascade: a MAPK kinase kinase (RAF), a MAPK kinase (MEK), and the terminal MAPK (ERK, JNK, or p38) [2]. Scaffold proteins, such as Kinase Suppressor of Ras (KSR), organize these kinases into functional units to ensure signaling specificity and efficiency within the cytoplasm and nucleus [3]. Dysregulation of these complexes, frequently through oncogenic mutations in upstream activators like KRAS or BRAF, is a hallmark of many human cancers, leading to uncontrolled cell growth and survival [4]. Consequently, components of these signaling complexes are major therapeutic targets, with numerous inhibitors of BRAF and MEK approved for clinical use, particularly in the treatment of melanoma and non-small cell lung cancer [5].

Other names

MAPK cascadeRAS-RAF-MEK-ERK pathwayERK signaling pathwayMitogen-activated protein kinase signaling networkMAPK/ERK pathway

Inhibition of kinase catalytic activity through ATP-competitive or allosteric binding, and disruption of protein-protein interactions or scaffolding within the signaling cascade [2, 4].