84-9363-19　Recombinant Human JNK2/MAPK9 Protein （His Tag） 500ug　PKSH031449

特徴

• 背景：Mitogen-activated protein kinase 9 （MAPK9）, also well known as c-Jun N-terminal kinase （JNK2）, is a member of MAP kinase subfamily belonging to the protein kinase superfamily.
• MAPK9 responds to activation by environmental stress and pro-inflammatory cytokines by phosphorylating a number of transcription factors, such as c-Jun and ATF2.
• The crystal structure of human JNK2 complexed with an indazole inhibitor by applying a high-throughput protein engineering and surface-site mutagenesis approach.
• A novel conformation of the activation loop is observed, which is not compatible with its phosphorylation by upstream kinases.
• This activation inhibitory conformation of JNK2 is stabilized by the MAP kinase insert that interacts with the activation loop in an induced-fit manner.
• It suggest that the MAP kinase insert of JNK2 plays a role in the regulation of JNK2 activation, possibly by interacting with intracellular binding partners.
• JNK2 deficiency leads to reduced c-Jun degradation, thereby augmenting c-Jun levels and cellular proliferation, and suggests that JNK2 is a negative regulator of cellular proliferation in multiple cell types.
• JNK2 prevents replicative stress by coordinating cell cycle progression and DNA damage repair mechanisms.
• JNK2 blocks the ubiquitination of tumor suppressor p53, and thus increases the stability of p53 in nonstressed cells.
• JNK2 negatively regulates antigen-specific CD8+ T cell expansion and effector function, and thus selectively blocking JNK2 in CD8+ T cells may potentially enhance anti-tumor immune response.
• Lack of JNK2 expression was associated with higher tumor aneuploidy and reduced DNA damage response.
• Additionally,the JNK2 protein could be a novel therapeutic target in dry eye disease, and may provide a novel target for prevention of vascular disease and atherosclerosis.