kinaseERK

ERK kinases, also known as extracellular signal-regulated kinases, are serine/threonine kinases that function in the MAPK signaling cascade. In humans, two main isoforms, ERK1 and ERK2, are encoded by MAPK3 and MAPK1 respectively. The kinases share high sequence similarity and are activated by dual phosphorylation on the activation loop TEY motif by MAP kinase kinases MEK1 and MEK2.

Activation occurs in response to growth factors, mitogens, and other stimuli that activate receptor tyrosine kinases, Ras, and Raf. Once activated, ERK1/2 translocate to the nucleus and cytoplasm, where they phosphorylate a wide range of substrates including transcription factors Elk-1, c-Fos, and ATF2, as well as proteins involved in translation and cytoskeletal dynamics such as RSK and others. Through these substrates ERK signaling promotes cell proliferation, differentiation, survival, and plasticity, and it participates in synaptic plasticity and learning in certain contexts.

Regulation is tight; activity is terminated by dual-specificity phosphatases (DUSPs/MKPs) and by feedback loops. Aberrant ERK signaling, due to mutations in upstream components or pathway amplification, is common in cancer and contributes to uncontrolled growth and resistance to apoptosis.

Therapeutic strategies target the pathway at different nodes; MEK inhibitors (e.g., trametinib) reduce ERK activation, while direct ERK inhibitors are under development; such agents are being explored in tumors with dysregulated MAPK signaling. The ERK pathway exemplifies a core signaling module with widespread roles in development, tissue homeostasis, and disease.