MAPK1

MAPK1, also known as ERK2, is a serine/threonine kinase that belongs to the mitogen-activated protein kinase (MAPK) family. It is a central component of the MAPK/ERK signaling cascade, which conveys mitogenic and differentiation signals from the cell surface to intracellular targets. Activation of ERK2 occurs through dual phosphorylation of the activation loop by MEK1/2, after which the active kinase can translocate to the nucleus and phosphorylate a range of substrates to influence gene expression and cellular behavior.

ERK2 responds to a variety of stimuli, including growth factors, cytokines, and other proliferative cues that activate the RAS-RAF-MEK-ERK axis. Once activated, ERK2 phosphorylates transcription factors such as ELK1 and other cytoplasmic targets, leading to the regulation of immediate early genes (for example, c-FOS and EGR1) and the promotion of cell cycle progression, differentiation, and survival in many cell types.

Regulation of MAPK1/ERK2 activity is achieved through both phosphorylation by upstream kinases and dephosphorylation by dual-specificity phosphatases (DUSPs). Scaffolding proteins, such as kinases suppressor of Ras (KSR), help organize the signaling module to ensure proper localization and signaling specificity.

Clinical and research relevance of MAPK1/ERK2 lies in its frequent involvement in cancer, where pathway hyperactivation can drive tumor growth. Therapeutic approaches include inhibitors targeting MEK or ERK to blunt signaling. ERK activity is also widely used as a biomarker to monitor pathway engagement in studies of cell biology and drug development. The protein is ubiquitously expressed and highly conserved across tissues.