MEK2

MEK2, or MAP kinase kinase 2, is a dual-specificity protein kinase that phosphorylates and activates extracellular signal-regulated kinases 1 and 2 (ERK1/2) within the MAPK/ERK signaling pathway. In humans it is encoded by the MAP2K2 gene and functions alongside MEK1 (MAP2K1) as a central kinase in transmitting signals from upstream mitogenic pathways to ERK targets that regulate gene expression and cellular behavior.

MEK2 sits downstream of Raf kinases in the Ras–Raf–MEK–ERK cascade and is activated by upstream signals such as growth factors. Once activated, MEK2 phosphorylates ERK1/2 on their activation loops, enabling ERK to regulate processes including cell proliferation, differentiation, migration, and survival. The MEK–ERK module is subject to tight regulation, with feedback mechanisms from ERK and scaffold proteins like KSR1/2 coordinating signaling output and specificity.

MAP2K2 can produce multiple isoforms through alternative splicing, resulting in variants that may differ in regulation or localization. In humans, MEK2 shares functional redundancy with MEK1 but both are important for proper MAPK signaling and can contribute to developmental processes when disrupted.

Clinical relevance centers on the role of MEK2 in diseases characterized by dysregulated MAPK signaling, particularly cancer. MEK inhibitors that target MEK1/2 have been approved for certain cancers, notably in combination therapies for BRAF-mutant melanoma. Agents in this class are used to prevent downstream ERK activation, though they can have side effects and may encounter resistance mechanisms. Ongoing research explores broader applications, resistance, and combination strategies to optimize therapeutic outcomes.