MAPK9

MAPK9, or mitogen-activated protein kinase 9, is a member of the MAP kinase family in humans. It encodes the JNK2 protein, a serine/threonine kinase in the c-Jun N-terminal kinase (JNK) subgroup, which also includes JNK1 (MAPK8) and JNK3 (MAPK10).

Activation of MAPK9 occurs through phosphorylation by upstream dual-specificity kinases MKK4 and MKK7 in response to cellular stress, inflammatory cytokines, UV irradiation, and other stimuli. Once activated, JNK2 phosphorylates substrates such as transcription factors c-Jun and ATF2, which modulate gene expression and drive diverse cellular responses including apoptosis, differentiation, and survival, depending on the cellular context.

Expression of MAPK9 is widespread across tissues, with notable levels in the brain and other organs. Although JNK1 and JNK3 have distinct tissue distributions and functions, JNK2 contributes to a broad range of stress responses in multiple cell types and can participate in overlapping or compensatory signaling with the other JNK family members.

Alterations in JNK signaling, including MAPK9 activity, have been linked to several diseases, such as neurodegenerative disorders, inflammatory conditions, and cancer. In neurons, JNK pathways can contribute to injury-induced apoptosis, while in other tissues they may influence cell proliferation, migration, or inflammatory responses.

MAPK9 activity is tightly regulated by phosphatases, including MAPK phosphatases (MKPs), and by scaffold proteins such as JNK-interacting proteins (JIPs) that assemble specific signaling complexes. This organization enables substrate specificity and efficient propagation of stress signals, making MAPK9 a focus of research into therapeutic strategies targeting the JNK pathway.