JNK1

JNK1, or c-Jun N-terminal kinase 1, is a serine/threonine protein kinase of the mitogen-activated protein kinase (MAPK) family. It is encoded by the MAPK8 gene in humans and belongs to the JNK subgroup that transduces signals in response to stress and cytokines. JNK1 is activated by upstream kinases MKK4 and MKK7 through phosphorylation of its activation loop at the Thr-Pro-Tyr motif.

Once activated, JNK1 phosphorylates a variety of substrates, including transcription factors such as c-Jun and ATF2, influencing gene expression. This can lead to changes in cell proliferation, differentiation, apoptosis, and inflammatory responses. JNK1 can reside in the cytoplasm or translocate to the nucleus, depending on the cellular context.

In humans, there are three JNK genes: MAPK8 (JNK1), MAPK9 (JNK2), and MAPK10 (JNK3). MAPK8 produces multiple isoforms via alternative splicing, such as JNK1alpha and JNK1beta, allowing some functional diversity. JNK1 is widely expressed across tissues, with notable presence in brain, liver, and muscle.

Physiologically, JNK1 participates in stress-induced apoptosis in certain contexts but can also promote survival, inflammation, and metabolic regulation depending on cell type and stimulus. In the nervous system, JNK1 is implicated in synaptic plasticity and neurodegenerative processes; in metabolic tissues, it is linked to insulin resistance; in cancer, JNK signaling can have pro- or anti-tumor effects according to context.

Regulation of JNK1 activity involves negative feedback by dual-specificity phosphatases (MKPs), such as DUSP1 (MKP-1), DUSP8, and DUSP10. In research, JNK1 inhibitors like SP600125 are used to study function, though specificity and off-target effects remain considerations.