Mitogen-activated protein kinase 1 (ERK2) (ERK2)

Mitogen-activated protein kinase 1 (MAPK1), widely known as ERK2, is a pivotal serine/threonine kinase within the Ras-Raf-MEK-ERK signaling cascade. It acts downstream of Ras, Raf, and MEK to relay extracellular signals—such as growth factors and cytokines—to the nucleus, where it phosphorylates numerous transcription factors to regulate cell proliferation, differentiation, and survival (UniProt: P28482). Dysregulation of the ERK pathway is a hallmark of various malignancies, often driven by oncogenic mutations in upstream components like KRAS or BRAF (PubMed: 30401435). Consequently, ERK2 has emerged as a significant therapeutic target, particularly for overcoming acquired resistance to BRAF and MEK inhibitors in cancers like melanoma and colorectal carcinoma (PubMed: 29213051). Current pharmacological strategies involve ATP-competitive small molecules that inhibit ERK1/2 activity to suppress tumor growth and induce apoptosis (PubMed: 25417113). Clinical development of these inhibitors focuses on their use as monotherapy or in combination with other MAPK pathway blockers to achieve more durable responses in patients with MAPK-driven tumors (ClinicalTrials.gov: NCT02296242).

Other names

MAPK1Extracellular signal-regulated kinase 2p42-MAPKPRKM1PRKM2Mitogen-activated protein kinase 2

Small molecule inhibition of the kinase catalytic activity, typically through ATP-competitive binding, which prevents the phosphorylation of downstream substrates and halts the signaling cascade.