Nuclear factor-kappa B, p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, and Extracellular signal-regulated kinase signaling pathways (NF-κB, p38, JNK, and ERK pathways)

The NF-κB, p38, JNK, and ERK signaling pathways represent a complex network of intracellular cascades that mediate cellular responses to inflammatory cytokines, growth factors, and environmental stressors (Zhang et al., 2017, Mediators of Inflammation). The NF-κB pathway is a primary regulator of the immune response and cell survival, centered on the translocation of Rel family transcription factors to the nucleus (Oeckinghaus & Ghosh, 2009, Cold Spring Harb Perspect Biol). The p38, JNK (c-Jun N-terminal kinase), and ERK (extracellular signal-regulated kinase) pathways constitute the three major branches of the Mitogen-Activated Protein Kinase (MAPK) superfamily, which transmit signals via sequential phosphorylation events (Kyriakis & Avruch, 2012, Physiol Rev). Together, these pathways coordinate the expression of genes involved in inflammation, proliferation, differentiation, and apoptosis (Arthur & Ley, 2013, Nat Rev Immunol). Aberrant activation of these signaling axes is strongly linked to the pathogenesis of chronic inflammatory disorders, autoimmune diseases, and many types of cancer (Kaminska, 2005, Biochim Biophys Acta). While many drugs, such as glucocorticoids and specific kinase inhibitors like Trametinib or Bortezomib, target components of these pathways, their broad physiological roles often lead to significant safety concerns and therapeutic index challenges (Dhillon et al., 2007, Cell Cycle).

Other names

MAPK and NF-κB signaling cascadesPro-inflammatory signaling pathwaysStress-activated protein kinase pathwaysMAPK/NF-κB network

Inhibition of upstream kinases such as MEK or IKK, competitive inhibition of ATP binding sites in MAPKs, or stabilization of inhibitory proteins like IκB to prevent transcription factor nuclear translocation.