MEK1 (MAP2K1)
MEK1, encoded by MAP2K1, is the dual-specificity kinase in the middle of the MAPK cascade that phosphorylates ERK in response to RAS-pathway signals.
Function
MEK1 sits between the RAF kinases and ERK. Activated BRAF phosphorylates MEK1 on two serines; MEK1 then phosphorylates ERK1/2 on both a threonine and a tyrosine - the dual specificity that gives the family its name. ERK carries the signal into the nucleus, where it phosphorylates transcription factors and drives the proliferative program. The cascade’s three-tiered structure (RAS → RAF → MEK → ERK) amplifies the signal at each step, and feedback phosphorylation from ERK back onto upstream components shapes the pathway’s dynamics.
In cancer
MAP2K1 carries activating mutations in a few percent of many tumors - melanoma, colorectal, lung - and is the escape route when upstream inhibitors fail: tumors treated with BRAF inhibitors acquire MEK mutations, and MEK inhibitors (trametinib, cobimetinib) are used in combination with BRAF inhibitors to close that route. MEK inhibition has broad toxicity because the pathway is active in normal proliferating tissue, which limits dosing.
Notes
- Human gene symbol: MAP2K1; UniProt Q02750; 393 amino acids; MAP kinase kinase (MKK) family.