ERK1

ERK1, or extracellular signal-regulated kinase 1, is a serine/threonine protein kinase in the MAP kinase signaling pathway. It is encoded by the MAPK3 gene in humans and forms part of the ERK1/ERK2 pair (the p44/p42 MAPKs) that relay signals from cell surface receptors to the nucleus to influence gene expression.

ERK1 is activated by dual phosphorylation on a threonine and a tyrosine residue within its activation loop by MEK1/2, in response to signals from receptor tyrosine kinases and the RAS-RAF-MEK cascade. Once active, ERK1 can translocate from the cytoplasm to the nucleus and phosphorylate a broad set of substrates, including transcription factors such as Elk-1 and c-Fos, as well as cytoplasmic kinases like RSK, leading to changes in gene expression and cellular behavior.

Functions of ERK1 include regulation of cell proliferation, differentiation, survival, and synaptic plasticity. It participates in responses to growth factors and stress and contributes to development and tissue homeostasis. In mammals, ERK1 and ERK2 have overlapping but distinct roles; in mice, Erk1 knockout animals are viable with some subtle defects, whereas Erk2 is essential for development, highlighting partial redundancy.

Regulation of ERK1 is achieved through phosphatases such as dual-specificity phosphatases (DUSPs) and feedback inhibitors, as well as scaffold proteins that organize signaling complexes. Dysregulation of ERK signaling is common in cancer and other diseases. Therapeutic strategies include inhibitors targeting MEK or RAF upstream, and direct ERK inhibitors are in development and clinical investigation. The MAPK3 gene designation and the alias ERK1 are widely used in human biology and disease research.