MAP2K1

MAP2K1, also known as MEK1, is a gene that encodes a dual specificity protein kinase involved in the mitogen-activated protein kinase (MAPK) signaling cascade. MEK1 is a central component of the extracellular signal–regulated kinase (ERK) pathway, acting downstream of RAF kinases and upstream of ERK1/2.

MEK1 functions as a kinase that phosphorylates ERK1 and ERK2 on specific threonine and tyrosine residues, thereby activating these kinases. Once activated, ERK1/2 translocate to the nucleus and regulate gene expression to influence cell proliferation, differentiation, survival, and other cellular processes. MEK1 activity is tightly regulated by upstream signals and scaffold proteins, and it participates in feedback regulation within the pathway.

In humans, MAP2K1 participates in diverse physiological processes due to the widespread importance of the MAPK/ERK pathway. It can be activated by receptor tyrosine kinases and Ras signaling, linking extracellular cues to transcriptional programs. The gene is expressed in multiple tissues, reflecting the broad role of ERK signaling in development and homeostasis.

Clinically, activating mutations in MAP2K1 have been found in a subset of diseases, including cancers and developmental disorders. Somatic MAP2K1 mutations are associated with Langerhans cell histiocytosis, and germline or mosaic alterations have been reported in conditions such as cardio-facio-cutaneous–like syndromes, reflecting the pathway’s role in development. MAP2K1 alterations often occur alongside other MAPK pathway mutations and can influence disease biology and treatment response.

Therapeutically, MEK1/MEK2 inhibitors (for example, trametinib and selumetinib) target the MAPK/ERK pathway and are used in tumors with dysregulated MEK activity due to MAP2K1 alterations or other pathway mutations, highlighting the clinical relevance of MAP2K1 as a drug target.