Mitogen-activated protein kinase kinase 1 (MEK1); Mitogen-activated protein kinase kinase 2 (MEK2) (MEK1; MEK2)

MEK1 and MEK2 are dual-specificity kinases integral to the MAPK/ERK signaling pathway. Their activation via phosphorylation by RAF kinases leads to the subsequent activation of ERK, which translocates to the nucleus and promotes gene expression for cell division and survival. Aberrations in this signaling cascade are common in tumors with BRAF or NRAS mutations, resulting in unchecked cell proliferation. Targeted drugs such as binimetinib (MEK inhibitor) are designed to bind MEK1/2 and prevent this overactive signaling, making these kinases critical therapeutic targets in oncology. Resistance mechanisms frequently arise from secondary MEK mutations or alternate pathway activation, complicating long-term efficacy. Biomarker-driven patient selection includes assessing BRAF and NRAS mutation status, pERK levels, and specific gene alterations. MEK inhibitors are generally well tolerated but require monitoring for class-specific adverse effects and resistance evolution.

Other names

Dual-specificity mitogen-activated protein kinase kinase 1 (MAP2K1)Dual-specificity mitogen-activated protein kinase kinase 2 (MAP2K2)MEK1MEK2

Inhibitors (like binimetinib) bind to non-ATP sites of MEK1/2 causing conformational inhibition, preventing ERK activation and downstream signaling needed for tumor cell proliferation and survival