MEK1

MEK1, or MAP kinase kinase 1, is a dual-specificity protein kinase that sits in the mitogen-activated protein kinase (MAPK) signaling pathway. It is encoded by the MAP2K1 gene in humans. MEK1 activates the downstream kinases ERK1 and ERK2 by phosphorylation, enabling them to regulate a wide range of cellular processes including proliferation, differentiation, and survival.

In the canonical RAF–MEK–ERK cascade, upstream signals from receptors and RAS activate RAF kinases, which then phosphorylate and activate MEK1. Once active, MEK1 phosphorylates ERK1/2 on specific serine/threonine and tyrosine residues, leading to ERK translocation to the nucleus and modulation of transcription factors and other substrates.

Regulation of MEK1 involves upstream signals from the RAS–RAF axis, as well as feedback mechanisms and phosphatases that modulate signaling intensity. MEK1 activity can be inhibited pharmacologically by MEK inhibitors, such as trametinib and selumetinib, which are used in targeted cancer therapies to dampen aberrant MAPK signaling in tumors with pathway activations.

Clinical significance of MAP2K1 includes associations between MEK1 mutations and developmental disorders such as cardio-facio-cutaneous syndrome and related Noonan-like syndromes, highlighting the role of MEK1 signaling in development. In cancer, activating alterations in the MAPK pathway commonly render tumors responsive to MEK inhibitors, underscoring the therapeutic relevance of MEK1 within the broader signaling network.