Extracellular signal-regulated kinase 1 (ERK1, MAPK3) and Extracellular signal-regulated kinase 2 (ERK2, MAPK1) (ERK1 (MAPK3), ERK2 (MAPK1))

Extracellular signal-regulated kinase 1 and 2 are highly conserved serine/threonine kinases, encoded by the MAPK3 and MAPK1 genes, respectively. They act as the final effectors in the canonical MAPK/ERK signaling cascade. Activated by upstream MEK1/2 kinases (which are in turn activated by Raf kinases in response to extracellular signals such as growth factors), ERK1/2 phosphorylate numerous cytoplasmic and nuclear substrates, including transcription factors (e.g., ELK1, c-Fos, JunB), cytoskeletal proteins, and additional regulatory molecules. ERK1/2 control critical cell functions such as cell cycle progression, survival, differentiation, migration, and transcription. Dysregulation of ERK1/2 activity is implicated in oncogenesis, making them key cancer therapeutic targets. Drugs targeting the MAPK/ERK pathway, directly or indirectly, are in clinical use and development, but their broad roles in normal cellular physiology pose notable toxicity and resistance challenges.

Other names

ERK1ERK2MAPK3 (for ERK1)MAPK1 (for ERK2)Extracellular signal-regulated kinase 1Extracellular signal-regulated kinase 2Mitogen-activated protein kinase 1/2p44 MAPK (ERK1)p42 MAPK (ERK2)

Inhibition of ERK1/2 phosphorylation (inhibiting kinase activity); Disruption of downstream transcription factor activation; Cell cycle arrest through cyclin-dependent kinase inhibitors