Mitogen-activated protein kinase 1

MAPK1 (mitogen-activated protein kinase 1, also called ERK2) is a serine/threonine kinase that serves as a central component of the MAP kinase signal transduction pathway (UniProt: P28482). It phosphorylates approximately 160 known substrates distributed across the nucleus, cytosol, and organelles, regulating diverse cellular processes including transcription, translation, cytoskeletal dynamics, mitosis, apoptosis, and endosomal trafficking. MAPK1 also functions as a transcriptional repressor independent of its kinase activity.

MAPK1 is widely expressed and participates in growth factor signaling cascades initiated by receptors such as KIT. In the context of genetic disease, mutations in MAPK1 cause Noonan syndrome 13, an autosomal dominant condition characterized by short stature, facial dysmorphic features, congenital heart defects, and developmental delays (UniProt: P28482).

MAPK1 is elevated in Alzheimer's disease brain tissue relative to age-matched controls in post-mortem samples analyzed by quantitative proteomics (Chaparral AD proteomics). The protein shows a mean log2 fold-change of 0.7765 in this dataset, indicating upregulation in the AD brain. This increased MAPK1 activity may reflect aberrant signaling responses to pathological features of neurodegeneration.