mitogen-activated protein kinase 8 (c-jun NH2 terminal kinase 1, MAPK8 JNK1, PRKM8, JNK46)

Function

• responds to activation by environmental stress & pro- inflammatory cytokines by phosphorylating a number of transcription factors, primarily components of AP-1 including c-Jun & ATF2 & thus regulates AP-1 transcriptional activity
• In T-cells, JNK1 & JNK2 are required for polarized differentiation of T-helper cells into Th1 cells (putative)
• phosphorylates heat shock factor protein 4 (HSF4)
• JNK1 isoforms display different binding patterns:
  • beta-1 preferentially binds to c-Jun
  • alpha-1, alpha-2, & beta-2 have a similar low level of binding to both c-Jun or ATF2
• no correlation between binding & phosphorylation, which is achieved at about the same efficiency by all isoforms
• binds to at least four scaffolding proteins, MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK8IP3/JIP-3/JSAP1 & SPAG9/MAPK8IP4/JIP-4
• these proteins also bind other components of the JNK signaling pathway
• interacts with TP53 & WWOX
• interacts with JAMP (putative)
• activated by Thr & Tyr phosphorylation by either of two dual specificity kinases, MAP2K4 & MAP2K7
• inhibited by dual specificity phosphatases, such as DUSP1
• dually phosphorylated on Thr-183 & Tyr-185, which activates the enzyme

Cofactor: Mg+2

Structure

• TXY motif contains the Thr & Tyr whose phosphorylation activates the MAP kinases
• belongs to the protein kinase superfamily, CMGC Ser/Thr protein kinase family, MAP kinase subfamily
• contains 1 protein kinase domain

More general terms

• c-jun NH2 terminal kinase, jun kinase (JNK) or stress-activated protein kinase (SAPK)

Database

• UniProt: http://www.uniprot.org/uniprot/P45983.html
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:5599
• OMIM: https://mirror.omim.org/entry/601158
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=5599