PhosphoERK

PhosphoERK, or phosphorylated ERK, denotes the activated form of extracellular signal-regulated kinase 1 and 2 (ERK1/ERK2), serine/threonine kinases in the MAPK signaling pathway. ERK1 and ERK2 are activated by dual phosphorylation on a conserved TEY activation loop by the upstream kinases MEK1 and MEK2 in response to mitogens, growth factors, hormones, and stress signals. Dual phosphorylation at threonine and tyrosine residues is required for full catalytic activity.

Activated ERK translocates to the nucleus and phosphorylates a set of transcription factors, including ELK1, SAP1, and c-Fos, leading to changes in gene expression that promote cell cycle progression, differentiation, and survival. ERK also phosphorylates cytoplasmic substrates involved in metabolism, cytoskeletal organization, and other signaling pathways. The phospho-status of ERK is commonly used as a readout of MAPK pathway activity in cell biology and biomedical research, typically detected by antibodies that recognize the dual-phosphorylated TEY motif, with bands corresponding to ERK1 and ERK2 around 44–46 kDa on Western blots.

Dysregulated ERK signaling can arise from activating mutations in upstream components such as RAS or RAF, or from aberrant receptor signaling, leading to sustained p-ERK and uncontrolled proliferation in many cancers. Conversely, targeted therapies that inhibit MEK or ERK reduce p-ERK levels and downstream signaling. The ERK family comprises ERK1 (MAPK3) and ERK2 (MAPK1), sharing high sequence similarity and overlapping functions, though some tissues and developmental contexts show isoform-specific roles.