Extracellular signal-regulated kinase (ERK) (ERK)

Extracellular signal-regulated kinase (ERK), specifically the isoforms ERK1 and ERK2, serves as the terminal node of the Ras-Raf-MEK-ERK mitogen-activated protein kinase (MAPK) signaling pathway (UniProt: P27361, P28482). This pathway is a fundamental mechanism by which cells convert extracellular stimuli, such as growth factors and cytokines, into intracellular responses including cell proliferation, differentiation, and survival (PubMed: 29439114). Upon activation by the dual-specificity kinase MEK, ERK translocates to the nucleus to phosphorylate and activate various transcription factors, thereby regulating gene expression (StatPearls: NBK554420). In many cancers, particularly those with mutations in BRAF or KRAS, the ERK pathway is hyperactivated, making it a high-priority target for oncology therapeutics (PubMed: 31110071). ERK inhibitors are currently being developed to address the limitations of upstream inhibitors, specifically to combat the emergence of resistance mechanisms that reactivate the MAPK pathway (ClinicalTrials.gov: NCT01787513).

Other names

MAPK1MAPK3ERK1ERK2p42 MAPKp44 MAPKMitogen-activated protein kinase 1Mitogen-activated protein kinase 3Microtubule-associated protein 2 kinase

Small molecule inhibition of ERK1 and ERK2 kinase activity, typically through ATP-competitive or non-competitive binding, to block downstream signaling in the MAPK pathway (PubMed: 29439114).