From Wikipedia, the free encyclopedia
Jump to: navigation, search
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 SPIB,[4] DUSP1,[5] Activating transcription factor 2,[6][7][8][9] SH3BP5,[10] GSTP1,[11] MAPK8IP1,[12][13] MAP2K7,[9][14] CRK,[15] MAP2K4,[8][9][14][16][17] DUSP22,[18] Myc,[19] MAP3K2,[14] DUSP10,[20] REL,[21] MAPK8IP3,[22][23] IRS1,[24][25] MAP3K1[26] and C-jun.[1][9][21][27][28][29][30][31]


  1. ^ a b Derijard B, Hibi M, Wu IH, Barrett T, Su B, Deng T, Karin M, Davis RJ (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 AJ, Cavanagh J, Sluss HK, Derijard B, Davis RJ (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. ^ Mao, C; Ray-Gallet D; Tavitian A; Moreau-Gachelin F (February 1996). "Differential phosphorylations of Spi-B and Spi-1 transcription factors". Oncogene (ENGLAND) 12 (4): 863–73. ISSN 0950-9232. PMID 8632909. 
  5. ^ Slack, D N; Seternes O M; Gabrielsen M; Keyse S M (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. (United States) 276 (19): 16491–500. doi:10.1074/jbc.M010966200. ISSN 0021-9258. PMID 11278799. 
  6. ^ Raingeaud, J; Gupta S; Rogers J S; Dickens M; Han J; Ulevitch R J; Davis R J (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. (UNITED STATES) 270 (13): 7420–6. doi:10.1074/jbc.270.13.7420. ISSN 0021-9258. PMID 7535770. 
  7. ^ Fuchs, S Y; Xie B; Adler V; Fried V A; Davis R J; Ronai Z (December 1997). "c-Jun NH2-terminal kinases target the ubiquitination of their associated transcription factors". J. Biol. Chem. (UNITED STATES) 272 (51): 32163–8. doi:10.1074/jbc.272.51.32163. ISSN 0021-9258. PMID 9405416. 
  8. ^ a b Chen, Z; Cobb M H (May 2001). "Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2". J. Biol. Chem. (United States) 276 (19): 16070–5. doi:10.1074/jbc.M100681200. ISSN 0021-9258. PMID 11279118. 
  9. ^ a b c d Tournier, C; Whitmarsh A J; Cavanagh J; Barrett T; Davis R J (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. (UNITED STATES) 94 (14): 7337–42. doi:10.1073/pnas.94.14.7337. ISSN 0027-8424. PMC 23822. PMID 9207092. 
  10. ^ Wiltshire, Carolyn; Matsushita Masato; Tsukada Satoshi; Gillespie David A F; May Gerhard H W (November 2002). "A new c-Jun N-terminal kinase (JNK)-interacting protein, Sab (SH3BP5), associates with mitochondria". Biochem. J. (England) 367 (Pt 3): 577–85. doi:10.1042/BJ20020553. ISSN 0264-6021. PMC 1222945. PMID 12167088. 
  11. ^ Wang, T; Arifoglu P; Ronai Z; Tew K D (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. (United States) 276 (24): 20999–1003. doi:10.1074/jbc.M101355200. ISSN 0021-9258. PMID 11279197. 
  12. ^ Whitmarsh, A J; Cavanagh J; Tournier C; Yasuda J; Davis R J (September 1998). "A mammalian scaffold complex that selectively mediates MAP kinase activation". Science (UNITED STATES) 281 (5383): 1671–4. doi:10.1126/science.281.5383.1671. ISSN 0036-8075. PMID 9767029. 
  13. ^ Cai, Yi; Lechner Mark S; Nihalani Deepak; Prindle Marc J; Holzman Lawrence B; Dressler Gregory R (January 2002). "Phosphorylation of Pax2 by the c-Jun N-terminal kinase and enhanced Pax2-dependent transcription activation". J. Biol. Chem. (United States) 277 (2): 1217–22. doi:10.1074/jbc.M109663200. ISSN 0021-9258. PMID 11700324. 
  14. ^ 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. (UNITED STATES) 20 (7): 2334–42. doi:10.1128/MCB.20.7.2334-2342.2000. ISSN 0270-7306. PMC 85399. PMID 10713157. 
  15. ^ Girardin, S E; Yaniv M (July 2001). "A direct interaction between JNK1 and CrkII is critical for Rac1-induced JNK activation". EMBO J. (England) 20 (13): 3437–46. doi:10.1093/emboj/20.13.3437. ISSN 0261-4189. PMC 125507. PMID 11432831. 
  16. ^ Lee, Clement M; Onésime Djamila; Reddy C Damodara; Dhanasekaran N; Reddy E Premkumar (October 2002). "JLP: A scaffolding protein that tethers JNK/p38MAPK signaling modules and transcription factors". Proc. Natl. Acad. Sci. U.S.A. (United States) 99 (22): 14189–94. doi:10.1073/pnas.232310199. ISSN 0027-8424. PMC 137859. PMID 12391307. 
  17. ^ Park, Hee-Sae; Kim Mi-Sung; Huh Sung-Ho; Park Jihyun; Chung Jongkyeong; Kang Sang Sun; Choi Eui-Ju (January 2002). "Akt (protein kinase B) negatively regulates SEK1 by means of protein phosphorylation". J. Biol. Chem. (United States) 277 (4): 2573–8. doi:10.1074/jbc.M110299200. ISSN 0021-9258. PMID 11707464. 
  18. ^ 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. (United States) 276 (29): 27575–83. doi:10.1074/jbc.M100408200. ISSN 0021-9258. PMID 11346645. 
  19. ^ 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. (UNITED STATES) 274 (46): 32580–7. doi:10.1074/jbc.274.46.32580. ISSN 0021-9258. PMID 10551811. 
  20. ^ Tanoue, T; Moriguchi T; Nishida E (July 1999). "Molecular cloning and characterization of a novel dual specificity phosphatase, MKP-5". J. Biol. Chem. (UNITED STATES) 274 (28): 19949–56. doi:10.1074/jbc.274.28.19949. ISSN 0021-9258. PMID 10391943. 
  21. ^ a b Meyer, C F; Wang X; Chang C; Templeton D; Tan T H (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. (UNITED STATES) 271 (15): 8971–6. doi:10.1074/jbc.271.15.8971. ISSN 0021-9258. PMID 8621542. 
  22. ^ Ito, M; Yoshioka K; Akechi M; Yamashita S; Takamatsu N; Sugiyama K; Hibi M; Nakabeppu Y; Shiba T; Yamamoto K I (November 1999). "JSAP1, a Novel June N-Terminal Protein Kinase (JNK)-Binding Protein That Functions as a Scaffold Factor in the JNK Signaling Pathway". Mol. Cell. Biol. (UNITED STATES) 19 (11): 7539–48. ISSN 0270-7306. PMC 84763. PMID 10523642. 
  23. ^ Kelkar, N; Gupta S; Dickens M; Davis R J (February 2000). "Interaction of a Mitogen-Activated Protein Kinase Signaling Module with the Neuronal Protein JIP3". Mol. Cell. Biol. (UNITED STATES) 20 (3): 1030–43. doi:10.1128/MCB.20.3.1030-1043.2000. ISSN 0270-7306. PMC 85220. PMID 10629060. 
  24. ^ Aguirre, Vincent; Werner Eric D; Giraud Jodel; Lee Yong Hee; Shoelson Steve E; White Morris F (January 2002). "Phosphorylation of Ser307 in insulin receptor substrate-1 blocks interactions with the insulin receptor and inhibits insulin action". J. Biol. Chem. (United States) 277 (2): 1531–7. doi:10.1074/jbc.M101521200. ISSN 0021-9258. PMID 11606564. 
  25. ^ Aguirre, V; Uchida T; Yenush L; Davis R; White M F (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. (UNITED STATES) 275 (12): 9047–54. doi:10.1074/jbc.275.12.9047. ISSN 0021-9258. PMID 10722755. 
  26. ^ Xu, S; Cobb M H (December 1997). "MEKK1 binds directly to the c-Jun N-terminal kinases/stress-activated protein kinases". J. Biol. Chem. (UNITED STATES) 272 (51): 32056–60. doi:10.1074/jbc.272.51.32056. ISSN 0021-9258. PMID 9405400. 
  27. ^ Ishitani, Tohru; Takaesu Giichi, Ninomiya-Tsuji Jun, Shibuya Hiroshi, Gaynor Richard B, Matsumoto Kunihiro (December 2003). "Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling". EMBO J. (England) 22 (23): 6277–88. doi:10.1093/emboj/cdg605. ISSN 0261-4189. PMC 291846. PMID 14633987. 
  28. ^ Nishitoh, H; Saitoh M; Mochida Y; Takeda K; Nakano H; Rothe M; Miyazono K; Ichijo H (September 1998). "ASK1 is essential for JNK/SAPK activation by TRAF2". Mol. Cell (UNITED STATES) 2 (3): 389–95. doi:10.1016/S1097-2765(00)80283-X. ISSN 1097-2765. PMID 9774977. 
  29. ^ Yazgan, Oya; Pfarr Curt M (August 2002). "Regulation of two JunD isoforms by June N-terminal kinases". J. Biol. Chem. (United States) 277 (33): 29710–8. doi:10.1074/jbc.M204552200. ISSN 0021-9258. PMID 12052834. 
  30. ^ Tada, K; Okazaki T, Sakon S, Kobarai T, Kurosawa K, Yamaoka S, Hashimoto H, Mak T W, Yagita H, Okumura K, Yeh W C, Nakano H (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. (United States) 276 (39): 36530–4. doi:10.1074/jbc.M104837200. ISSN 0021-9258. PMID 11479302. 
  31. ^ Cano, E; Hazzalin C A; Kardalinou E; Buckle R S; Mahadevan L C (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. (ENGLAND) 108 (11): 3599–609. ISSN 0021-9533. PMID 8586671. 

External links[edit]

Further reading[edit]

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