Mitogen-activated protein kinase kinase 1 (for MEK1), Mitogen-activated protein kinase kinase 2 (for MEK2) (MEK1 (MAP2K1), MEK2 (MAP2K2))

Mitogen-activated protein kinase kinase 1 (MEK1) and Mitogen-activated protein kinase kinase 2 (MEK2) are closely related dual-specificity kinases that are critical components of the RAS-RAF-MEK-ERK signal transduction pathway, mediating cellular responses such as proliferation, survival, and differentiation[1][2][5]. These enzymes catalyze the phosphorylation and activation of extracellular signal-regulated kinases (ERK1/2) in response to various mitogenic and stress signals, playing a pivotal role in development and homeostasis[1][3][4][6]. Aberrant activation of MEK1/2, often due to upstream oncogenic mutations in RAS or BRAF, is implicated in the pathogenesis of many cancers and developmental disorders[1][2][3]. MEK1/2 are therapeutic targets for a class of anticancer agents (MEK inhibitors) used especially in melanomas and other cancers driven by MAPK pathway mutations, with approved drugs including trametinib, cobimetinib, and binimetinib[2][5]. Inhibition of MEK1/2 leads to decreased ERK1/2 activation, suppression of tumor cell growth, and induction of apoptosis, but long-term treatment is limited by toxicity and resistance mechanisms.

Other names

MEK1MEK2MAP2K1MAP2K2MAPKK1MAPKK2MAP kinase kinase 1MAP kinase kinase 2Dual-specificity mitogen-activated protein kinase kinase 1/2

Inhibition of MEK1/2 kinase activity, leading to suppression of ERK1/2 signaling and downstream cellular proliferation Allosteric inhibition (non-ATP competitive binding) Induction of cell cycle arrest and/or apoptosis in cancer cells