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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

Interactions

molecular events

Related

mitogen-activated protein kinase 8 Ag in tissue

General

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

Properties

SIZE: entity length = 427 aa MW = 48 kD COMPARTMENT: cytoplasm STATE: active state MOTIF: kinase domain SITE: 26-321 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 32-40 ATP-binding site NAME: ATP-binding site SITE: 55-55 aspartate residue {D151} TXY {183-185} Thr phosphorylation site {T183} Tyr phosphorylation site {Y185} Thr phosphorylation site {T255} Thr phosphorylation site {T258} Tyr phosphorylation site {Y259} Tyr phosphorylation site {Y357} Thr phosphorylation site {T367} Ser phosphorylation site {S377}

References

  1. Drijard B et al. JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain. Cell. 1994 Mar 25;76(6):1025-37. PMID: 8137421
  2. Lin A, Minden A, Martinetto H, Claret FX, Lange-Carter C, Mercurio F, Johnson GL, Karin M. Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2. Science. 1995 Apr 14;268(5208):286-90. PMID: 7716521
  3. Atlas of genetics & cytogenetics in oncology & Haematology http://atlasgeneticsoncology.org/genes/JNK1ID196.html
  4. Wikipedia; Note: C-Jun N-terminal kinases entry http://en.wikipedia.org/wiki/C-Jun_N-terminal_kinase
  5. UniProt :accession P45983

Databases & Figures

OMIM 601158 UniProt P45983 Pfam PF00069 Entrez Gene 5599 Kegg hsa:5599 ENZYME 2.7.11.24 MAP kinase pathways