MEK

Mitogen-activated protein kinase kinase (MEK), primarily represented by MEK1 (MAP2K1) and MEK2 (MAP2K2), is a dual-specificity protein kinase that phosphorylates and activates extracellular signal-regulated kinases ERK1 and ERK2, thereby functioning as a central signaling relay within the MAPK/ERK cascade^[1][2]. MEK operates downstream of RAS and RAF kinases and transduces extracellular and intracellular signals into programs controlling cell proliferation, differentiation, survival, transcriptional regulation, and development^[2][3][4]. Mechanistically, RAF-mediated activation of MEK enables phosphorylation of ERK proteins at the conserved Thr-Glu-Tyr motif, leading to signal propagation through the canonical MAPK pathway^[2][5]. Aberrant activation of MEK signaling has been associated with multiple human diseases, including melanoma, lung cancer, ovarian cancer, leukemia, lymphoma, and developmental disorders linked to dysregulated RAS/MAPK signaling^[2][6][7]. Compared with other MAP2K family members that regulate the p38 or JNK pathways, MEK1 and MEK2 function specifically within the ERK signaling branch, providing pathway selectivity and making them key experimental targets for dissecting MAPK-dependent biological responses^[1]. For experimental applications, pharmacological MEK inhibitors including trametinib, selumetinib, cobimetinib, binimetinib, mirdametinib, and avutometinib are widely used to suppress ERK activation and investigate MEK-dependent signaling mechanisms in cancer and developmental biology models^[2].