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Mitogen-activated protein kinase 8
Protein MAPK8 PDB 1jnk.png
PDB rendering based on 1jnk.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols MAPK8 ; JNK; JNK-46; JNK1; JNK1A2; JNK21B1/2; PRKM8; SAPK1; SAPK1c
External IDs OMIM601158 MGI1346861 HomoloGene56760 ChEMBL: 2276 GeneCards: MAPK8 Gene
EC number
RNA expression pattern
PBB GE MAPK8 210671 x at tn.png
PBB GE MAPK8 210477 x at tn.png
More reference expression data
Species Human Mouse
Entrez 5599 26419
Ensembl ENSG00000107643 ENSMUSG00000021936
UniProt P45983 Q91Y86
RefSeq (mRNA) NM_001278547 NM_016700
RefSeq (protein) NP_001265476 NP_057909
Location (UCSC) Chr 10:
49.51 – 49.65 Mb
Chr 14:
33.38 – 33.45 Mb
PubMed search [1] [2]

Mitogen-activated protein kinase 8 (also known as JNK1) is an enzyme that in humans is encoded by the MAPK8 gene.[1][2]


The protein encoded by this gene is a member of the MAP kinase and JNK family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is activated by various cell stimuli, and targets specific transcription factors, and thus mediates immediate-early gene expression in response to cell stimuli. The activation of this kinase by tumor-necrosis factor alpha (TNF-alpha) is found to be required for TNF-alpha-induced apoptosis. This kinase is also involved in UV radiation-induced apoptosis, which is thought to be related to the cytochrome c-mediated cell death pathway. Studies of the mouse counterpart of this gene suggested that this kinase play a key role in T cell proliferation, apoptosis and differentiation. Four alternately spliced transcript variants encoding distinct isoforms have been reported.[3]


MAPK8 has been shown to interact with:


  1. ^ a b Dérijard B, Hibi M, Wu I, Barrett T, Su B, Deng T et al. (April 1994). "JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain". Cell 76 (6): 1025–37. doi:10.1016/0092-8674(94)90380-8. PMID 8137421. 
  2. ^ Gupta S, Barrett T, Whitmarsh A, Cavanagh J, Sluss H, Dérijard B et al. (July 1996). "Selective interaction of JNK protein kinase isoforms with transcription factors". EMBO J. 15 (11): 2760–70. PMC 450211. PMID 8654373. 
  3. ^ "Entrez Gene: MAPK8 mitogen-activated protein kinase 8". 
  4. ^ Raingeaud J, Gupta S, Rogers J, Dickens M, Han J, Ulevitch R et al. (March 1995). "Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine". J. Biol. Chem. 270 (13): 7420–6. PMID 7535770. 
  5. ^ Fuchs S, Xie B, Adler V, Fried V, Davis R, Ronai Z (December 1997). "c-Jun NH2-terminal kinases target the ubiquitination of their associated transcription factors". J. Biol. Chem. 272 (51): 32163–8. PMID 9405416. 
  6. ^ a b Chen Z, Cobb M (May 2001). "Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2". J. Biol. Chem. 276 (19): 16070–5. doi:10.1074/jbc.M100681200. PMID 11279118. 
  7. ^ a b c d Tournier C, Whitmarsh A, Cavanagh J, Barrett T, Davis R (July 1997). "Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proc. Natl. Acad. Sci. U.S.A. 94 (14): 7337–42. PMC 23822. PMID 9207092. 
  8. ^ a b Meyer C, Wang X, Chang C, Templeton D, Tan T (April 1996). "Interaction between c-Rel and the mitogen-activated protein kinase kinase kinase 1 signaling cascade in mediating kappaB enhancer activation". J. Biol. Chem. 271 (15): 8971–6. PMID 8621542. 
  9. ^ Ishitani T, Takaesu G, Ninomiya-Tsuji J, Shibuya H, Gaynor R, Matsumoto K (December 2003). "Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling". EMBO J. 22 (23): 6277–88. doi:10.1093/emboj/cdg605. PMC 291846. PMID 14633987. 
  10. ^ Nishitoh H, Saitoh M, Mochida Y, Takeda K, Nakano H, Rothe M et al. (September 1998). "ASK1 is essential for JNK/SAPK activation by TRAF2". Mol. Cell 2 (3): 389–95. PMID 9774977. 
  11. ^ Yazgan O, Pfarr C (August 2002). "Regulation of two JunD isoforms by Jun N-terminal kinases". J. Biol. Chem. 277 (33): 29710–8. doi:10.1074/jbc.M204552200. PMID 12052834. 
  12. ^ Tada K, Okazaki T, Sakon S, Kobarai T, Kurosawa K, Yamaoka S et al. (September 2001). "Critical roles of TRAF2 and TRAF5 in tumor necrosis factor-induced NF-kappa B activation and protection from cell death". J. Biol. Chem. 276 (39): 36530–4. doi:10.1074/jbc.M104837200. PMID 11479302. 
  13. ^ Cano E, Hazzalin C, Kardalinou E, Buckle R, Mahadevan L (November 1995). "Neither ERK nor JNK/SAPK MAP kinase subtypes are essential for histone H3/HMG-14 phosphorylation or c-fos and c-jun induction". J. Cell. Sci. 108 ( Pt 11): 3599–609. PMID 8586671. 
  14. ^ Girardin S, Yaniv M (July 2001). "A direct interaction between JNK1 and CrkII is critical for Rac1-induced JNK activation". EMBO J. 20 (13): 3437–46. doi:10.1093/emboj/20.13.3437. PMC 125507. PMID 11432831. 
  15. ^ Tanoue T, Moriguchi T, Nishida E (July 1999). "Molecular cloning and characterization of a novel dual specificity phosphatase, MKP-5". J. Biol. Chem. 274 (28): 19949–56. PMID 10391943. 
  16. ^ Slack D, Seternes O, Gabrielsen M, Keyse S (May 2001). "Distinct binding determinants for ERK2/p38alpha and JNK map kinases mediate catalytic activation and substrate selectivity of map kinase phosphatase-1". J. Biol. Chem. 276 (19): 16491–500. doi:10.1074/jbc.M010966200. PMID 11278799. 
  17. ^ Aoyama K, Nagata M, Oshima K, Matsuda T, Aoki N (July 2001). "Molecular cloning and characterization of a novel dual specificity phosphatase, LMW-DSP2, that lacks the cdc25 homology domain". J. Biol. Chem. 276 (29): 27575–83. doi:10.1074/jbc.M100408200. PMID 11346645. 
  18. ^ Wang T, Arifoglu P, Ronai Z, Tew K (June 2001). "Glutathione S-transferase P1-1 (GSTP1-1) inhibits c-Jun N-terminal kinase (JNK1) signaling through interaction with the C terminus". J. Biol. Chem. 276 (24): 20999–1003. doi:10.1074/jbc.M101355200. PMID 11279197. 
  19. ^ Aguirre V, Werner E, Giraud J, Lee Y, Shoelson S, White M (January 2002). "Phosphorylation of Ser307 in insulin receptor substrate-1 blocks interactions with the insulin receptor and inhibits insulin action". J. Biol. Chem. 277 (2): 1531–7. doi:10.1074/jbc.M101521200. PMID 11606564. 
  20. ^ Aguirre V, Uchida T, Yenush L, Davis R, White M (March 2000). "The c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307)". J. Biol. Chem. 275 (12): 9047–54. PMID 10722755. 
  21. ^ a b c Cheng J, Yang J, Xia Y, Karin M, Su B (April 2000). "Synergistic interaction of MEK kinase 2, c-Jun N-terminal kinase (JNK) kinase 2, and JNK1 results in efficient and specific JNK1 activation". Mol. Cell. Biol. 20 (7): 2334–42. PMC 85399. PMID 10713157. 
  22. ^ Lee C, Onésime D, Reddy C, Dhanasekaran N, Reddy E (October 2002). "JLP: A scaffolding protein that tethers JNK/p38MAPK signaling modules and transcription factors". Proc. Natl. Acad. Sci. U.S.A. 99 (22): 14189–94. doi:10.1073/pnas.232310199. PMC 137859. PMID 12391307. 
  23. ^ Park H, Kim M, Huh S, Park J, Chung J, Kang S et al. (January 2002). "Akt (protein kinase B) negatively regulates SEK1 by means of protein phosphorylation". J. Biol. Chem. 277 (4): 2573–8. doi:10.1074/jbc.M110299200. PMID 11707464. 
  24. ^ Xu S, Cobb M (December 1997). "MEKK1 binds directly to the c-Jun N-terminal kinases/stress-activated protein kinases". J. Biol. Chem. 272 (51): 32056–60. PMID 9405400. 
  25. ^ Elion E (September 1998). "Routing MAP kinase cascades". Science 281 (5383): 1625–6. PMID 9767029. 
  26. ^ Cai Y, Lechner M, Nihalani D, Prindle M, Holzman L, Dressler G (January 2002). "Phosphorylation of Pax2 by the c-Jun N-terminal kinase and enhanced Pax2-dependent transcription activation". J. Biol. Chem. 277 (2): 1217–22. doi:10.1074/jbc.M109663200. PMID 11700324. 
  27. ^ Ito M, Yoshioka K, Akechi M, Yamashita S, Takamatsu N, Sugiyama K et al. (November 1999). "JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a Scaffold factor in the JNK signaling pathway". Mol. Cell. Biol. 19 (11): 7539–48. PMC 84763. PMID 10523642. 
  28. ^ Kelkar N, Gupta S, Dickens M, Davis R (February 2000). "Interaction of a mitogen-activated protein kinase signaling module with the neuronal protein JIP3". Mol. Cell. Biol. 20 (3): 1030–43. PMC 85220. PMID 10629060. 
  29. ^ Noguchi K, Kitanaka C, Yamana H, Kokubu A, Mochizuki T, Kuchino Y (November 1999). "Regulation of c-Myc through phosphorylation at Ser-62 and Ser-71 by c-Jun N-terminal kinase". J. Biol. Chem. 274 (46): 32580–7. PMID 10551811. 
  30. ^ Wiltshire C, Matsushita M, Tsukada S, Gillespie D, May G (November 2002). "A new c-Jun N-terminal kinase (JNK)-interacting protein, Sab (SH3BP5), associates with mitochondria". Biochem. J. 367 (Pt 3): 577–85. doi:10.1042/BJ20020553. PMC 1222945. PMID 12167088. 
  31. ^ Mao C, Ray-Gallet D, Tavitian A, Moreau-Gachelin F (February 1996). "Differential phosphorylations of Spi-B and Spi-1 transcription factors". Oncogene 12 (4): 863–73. PMID 8632909. 

Further reading[edit]

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.