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

Extracellular signal-regulated kinase 1 (ERK1; MAPK3) and extracellular signal-regulated kinase 2 (ERK2; MAPK1) are highly homologous serine/threonine protein kinases that are central components of the Ras-Raf-MEK-ERK (MAPK) signaling cascade, which transduces signals from cell surface receptors to the nucleus and orchestrates critical processes such as cell proliferation, differentiation, survival, and migration[1][5][7]. ERK1/2 are activated by dual phosphorylation through MEK1/2 and, in turn, phosphorylate a broad range of cytoplasmic and nuclear substrates including transcription factors, metabolic enzymes, and cytoskeletal proteins[1][3]. Dysregulation and hyperactivation of the ERK1/2 pathway are implicated in a wide spectrum of diseases, especially cancer, where mutations in upstream components lead to persistent ERK signaling[1][5][6]. ERK1/2 inhibitors are being developed as targeted therapies, particularly to overcome resistance to inhibitors of upstream kinases (RAS, RAF, MEK)[6]. However, given their fundamental role in normal cellular physiology, therapeutic targeting of ERK1/2 presents challenges related to toxicity and resistance mechanisms[1][6].

Other names

MAPK3 (for ERK1)MAPK1 (for ERK2)ERKsMitogen-activated protein kinase 1/3p44 MAPK (ERK1)p42 MAPK (ERK2)Classical MAP kinases

Small-molecule inhibition of kinase activity (ATP-competitive or allosteric) Suppression of phosphorylation of downstream substrates in the MAPK pathway