Mitogen-activated protein kinase 3

Mitogen-activated protein kinase 3 (MAPK3, also called ERK1) is a serine/threonine kinase that functions as a core component of the MAPK/ERK signal transduction cascade (UniProt: P27361). It regulates diverse cellular processes including growth, survival, differentiation, and apoptosis through phosphorylation of over 160 known substrates—including transcription factors, cytoskeletal proteins, translation regulators, and other signaling molecules. The MAPK/ERK pathway also governs endosomal dynamics, lysosome processing, and Golgi fragmentation during mitosis.

MAPK3 is widely expressed and participates in fundamental cellular processes across tissues. No specific disease associations are documented in UniProt for this entry, though the MAPK/ERK cascade is known to be dysregulated in various pathological contexts.

In Alzheimer's Disease, MAPK3 is downregulated in post-mortem brain tissue compared to age-matched controls (mean log2 fold-change = −0.50; Chaparral AD proteomics). This reduction was detected via TMT-labeled proteomics across four subcellular fractions (P2, P3, S2, S3) from human AD brain homogenates, suggesting impaired MAPK3-dependent signaling may contribute to AD pathology.