c-Jun N-terminal kinase and Extracellular signal-regulated kinase (JNK and ERK)

c-Jun N-terminal kinase (JNK) and Extracellular signal-regulated kinase (ERK) are two distinct subfamilies of the Mitogen-Activated Protein Kinase (MAPK) signaling network that regulate critical cellular processes. JNKs, also known as stress-activated protein kinases (SAPKs), are primarily activated by environmental stressors, such as UV radiation and heat shock, as well as pro-inflammatory cytokines, playing a pivotal role in apoptosis and the inflammatory response (UniProt: P45983; NIH: PMC4549119). In contrast, ERKs are the terminal effectors of the Ras-Raf-MEK-ERK cascade, typically activated by growth factors and mitogens to drive cell proliferation, survival, and differentiation (UniProt: P27361; StatPearls: NBK557544). Dysregulation of these pathways is frequently observed in human pathologies; ERK overactivation is a hallmark of many solid tumors, while aberrant JNK signaling is implicated in chronic inflammatory diseases, metabolic disorders like type 2 diabetes, and neurodegeneration (PubMed: 25847248). Therapeutic targeting of these kinases involves small-molecule inhibitors designed to block their enzymatic activity, although clinical success is often challenged by the high degree of pathway crosstalk, systemic toxicity, and the rapid emergence of resistance mechanisms (PubMed: 30356010).

Other names

Mitogen-activated protein kinase (MAPK)Stress-activated protein kinase (SAPK)MAPK8/9/10 (JNK)MAPK1/3 (ERK)JNK1/2/3ERK1/2

Inhibition of kinase catalytic activity by competing with ATP for the binding site or through allosteric modulation, thereby preventing the phosphorylation of downstream substrates such as c-Jun, RSK, and various transcription factors (PubMed: 30356010; UniProt: P45983).