C-Jun N-terminal kinases

Overview
C-Jun N-terminal kinases (JNKs), originally identified as kinases that bind and phosphosphorylate c-Jun on Ser63 and Ser73 within its transcriptional activation domain, are mitogen-activated protein kinases which are responsive to stress stimuli, such as cytokines, ultraviolet irradiation, heat shock, and osmotic shock, and are involved in T cell differentiation and apoptosis.

Isoforms
The c-Jun N-terminal kinases consist of ten isoforms deriving from the three genes JNK1, JNK2 and JNK3 :
 * JNK1 and JNK2 are ubiquitously distributed.
 * By contrast, JNK3 is found mainly in neuronal tissue and testes.

Functions
JNK1 is involved in apoptosis, neurodegeneration, cell differentiation and proliferation, inflammatory conditions and cytokine production mediated by AP-1 (Activation Protein 1) such as RANTES, IL-8 and GM-CSF.

Recently, JNK1 has been found to regulate Jun protein turnover by phosphorylation and activation of the ubiquitin ligase Itch.

JNKs can associate with scaffold proteins JNK Interacting Proteins as well as their upstream kinases JNKK1 and JNKK2 following their activation.