Mitogen-activated protein kinase 8 (MAPK8) and p38 mitogen-activated protein kinase (p38 MAPK) (MAPK8/JNK and p38 MAPK)

Mitogen-activated protein kinase 8 (MAPK8, also known as JNK1) and the p38 mitogen-activated protein kinase (MAPK) family are key components of the stress-activated protein kinase (SAPK) signaling pathways. These enzymes are activated in response to a variety of environmental stresses, such as UV radiation and osmotic shock, as well as inflammatory cytokines like TNF-alpha and IL-1beta (UniProt P45983, Q16539). Once activated, they phosphorylate a range of transcription factors, including c-Jun and ATF2, which regulate genes involved in apoptosis, cell differentiation, and the immune response (PubMed: 29334061). In pathological conditions, overactivation of JNK and p38 is linked to chronic inflammatory diseases, such as rheumatoid arthritis and Crohn's disease, as well as neurodegeneration and various cancers (PubMed: 25816698). Pharmaceutical research has focused on developing small-molecule inhibitors to block these kinases, aiming to suppress the production of pro-inflammatory cytokines. Despite their potential, many candidates have faced hurdles in clinical trials due to off-target toxicities and the essential roles these kinases play in normal physiological homeostasis (PubMed: 30213481).

Other names

JNK1c-Jun N-terminal kinase 1SAPK1SAPK2MAPK14CSBPRKStress-activated protein kinase

Inhibition of kinase catalytic activity through ATP-competitive or allosteric binding, preventing the phosphorylation of downstream substrates such as c-Jun and ATF2.