Mitogen-activated protein kinase 1 (for ERK2) and Mitogen-activated protein kinase 3 (for ERK1) (ERK1 (MAPK3), ERK2 (MAPK1))

The mitogen‑activated protein kinases known as extracellular signal‑regulated kinases (ERKs) are serine/threonine kinases that play a central role in relaying signals from growth factors and other extracellular stimuli through a cascade known as the Ras-Raf-MEK‑ERK pathway, ultimately influencing gene expression within the nucleus. Activation typically begins with ligand binding at receptor tyrosine kinases such as EGFR, followed by sequential activation through Ras GTPase, Raf kinases, MEKs, then finally ERKs, which phosphorylate various nuclear targets including transcription factors. Dysregulation—often via mutation—of this cascade is implicated in many cancers and developmental syndromes ("RASopathies"), making these proteins major drug targets. Numerous small-molecule inhibitors have been developed against different components including direct ERK inhibitors, some now approved or under clinical investigation for cancer treatment. However, adaptive resistance remains a significant challenge due to feedback loops and alternative pathways within this complex signaling network.

Other names

Extracellular signal-regulated kinaseMAP kinaseMAPKERT1/ERT2p44/p42 MAP Kinase

Inhibition of phosphorylation/catalytic activity of ERKs Blockade of downstream signal transduction leading to reduced proliferation/survival signals in cancer cells