MAPK8

Mitogen-activated protein kinase 8 (also known as JNK1) is a ubiquitous enzyme that in humans is encoded by the MAPK8 gene.[5][6]

MAPK8
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1UKH, 1UKI, 2G01, 2GMX, 2H96, 2NO3, 2XRW, 2XS0, 3ELJ, 3O17, 3O2M, 3PZE, 3V3V, 3VUD, 3VUG, 3VUH, 3VUI, 3VUK, 3VUL, 3VUM, 4AWI, 4E73, 4G1W, 4HYS, 4HYU, 4IZY, 4L7F, 4QTD, 4UX9, 4YR8
Identifiers
Aliases	MAPK8, Mapk8, AI849689, JNK, JNK1, Prkm8, SAPK1, JNK-46, JNK1A2, JNK21B1/2, SAPK1c, mitogen-activated protein kinase 8
External IDs	OMIM: 601158 MGI: 1346861 HomoloGene: 56760 GeneCards: MAPK8
Gene location (Human) Chr. Chromosome 10 (human)[1] Band 10q11.22 Start 48,306,639 bp[1] End 48,439,360 bp[1]
Gene location (Mouse) Chr. Chromosome 14 (mouse)[2] Band 14|14 B Start 33,377,898 bp[2] End 33,447,158 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • transferase activity • nucleotide binding • protein kinase activity • MAP kinase activity • histone deacetylase binding • histone deacetylase regulator activity • protein serine/threonine kinase activity • GO:0001948 protein binding • enzyme binding • ATP binding • JUN kinase activity • kinase activity Cellular component • cytosol • nucleoplasm • cell nucleus • mitochondrion • cytoplasm • neuron projection • axon • basilar dendrite Biological process • phosphorylation • rhythmic process • response to stress • negative regulation of apoptotic process • negative regulation of protein binding • positive regulation of protein metabolic process • regulation of protein localization • Fc-epsilon receptor signaling pathway • JNK cascade • cellular response to mechanical stimulus • positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway • positive regulation of gene expression • JUN phosphorylation • regulation of sequence-specific DNA binding transcription factor activity • peptidyl-serine phosphorylation • regulation of circadian rhythm • positive regulation of deacetylase activity • peptidyl-threonine phosphorylation • positive regulation of cyclase activity • cellular response to lipopolysaccharide • response to UV • regulation of macroautophagy • regulation of histone deacetylation • positive regulation of apoptotic process • neuron development • protein phosphorylation • cellular response to amino acid starvation • cellular response to reactive oxygen species • stress-activated MAPK cascade • cellular response to cadmium ion • regulation of DNA replication origin binding • response to mechanical stimulus • regulation of gene expression • GO:0007243 intracellular signal transduction • cellular response to organic substance • cellular response to cytokine stimulus Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	5599	26419
Ensembl	ENSG00000107643	ENSMUSG00000021936
UniProt	P45983	Q91Y86
RefSeq (mRNA)	NM_001278547 NM_001278548 NM_002750 NM_139046 NM_139049 NM_001323302 NM_001323320 NM_001323321 NM_001323322 NM_001323323 NM_001323324 NM_001323325 NM_001323326 NM_001323327 NM_001323328 NM_001323329 NM_001323330 NM_001323331	NM_001310452 NM_001310453 NM_001310454 NM_016700
RefSeq (protein)	NP_001265476 NP_001265477 NP_001310231 NP_001310249 NP_001310250 NP_001310251 NP_001310252 NP_001310253 NP_001310254 NP_001310255 NP_001310256 NP_001310257 NP_001310258 NP_001310259 NP_001310260 NP_620634 NP_620637	NP_001297381 NP_001297382 NP_001297383 NP_057909
Location (UCSC)	Chr 10: 48.31 – 48.44 Mb	Chr 14: 33.38 – 33.45 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

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.[7] MAPK8 contains multiple amino acid sites that are phosphorylated and ubiquitinated.[8]

Interactions

MAPK8 has been shown to interact with:

• Activating transcription factor 2,[9][10][11][12]
• C-jun,[5][12][13][14][15][16][17][18]
• CRK,[19]
• DUSP10,[20]
• DUSP1,[21]
• DUSP22,[22]
• GSTP1,[23]
• IRS1,[24][25]
• ITCH, [26][27]
• MAP2K4,[11][12][28][29][30]
• MAP2K7,[12][28]
• MAP3K1[31]
• MAP3K2,[28]
• MAPK8IP1,[32][33]
• MAPK8IP3,[34][35]
• Myc,[36]
• REL,[13]
• SH3BP5,[37] and
• SPIB.[38]

References

1. GRCh38: Ensembl release 89: ENSG00000107643 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000021936 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Dérijard 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. S2CID 6797795.
6. Gupta S, Barrett T, Whitmarsh AJ, Cavanagh J, Sluss HK, Dérijard B, Davis RJ (July 1996). "Selective interaction of JNK protein kinase isoforms with transcription factors". EMBO J. 15 (11): 2760–70. doi:10.1002/j.1460-2075.1996.tb00636.x. PMC 450211. PMID 8654373.
7. "Entrez Gene: MAPK8 mitogen-activated protein kinase 8".
8. "JNK1 (human)". www.phosphosite.org. Retrieved 2020-10-28.
9. Raingeaud J, Gupta S, Rogers JS, Dickens M, Han J, Ulevitch RJ, Davis RJ (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. doi:10.1074/jbc.270.13.7420. PMID 7535770.
10. Fuchs SY, Xie B, Adler V, Fried VA, Davis RJ, Ronai Z (December 1997). "c-Jun NH2-terminal kinases target the ubiquitination of their associated transcription factors". J. Biol. Chem. 272 (51): 32163–8. doi:10.1074/jbc.272.51.32163. PMID 9405416.
11. Chen Z, Cobb MH (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.
12. Tournier C, Whitmarsh AJ, Cavanagh J, Barrett T, Davis RJ (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. doi:10.1073/pnas.94.14.7337. PMC 23822. PMID 9207092.
13. Meyer CF, Wang X, Chang C, Templeton D, Tan TH (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. doi:10.1074/jbc.271.15.8971. PMID 8621542.
14. Ishitani T, Takaesu G, Ninomiya-Tsuji J, Shibuya H, Gaynor RB, 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.
15. 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. 2 (3): 389–95. doi:10.1016/s1097-2765(00)80283-x. PMID 9774977.
16. Yazgan O, Pfarr CM (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.
17. Tada K, Okazaki T, Sakon S, Kobarai T, Kurosawa K, Yamaoka S, Hashimoto H, Mak TW, Yagita H, Okumura K, Yeh WC, 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. 276 (39): 36530–4. doi:10.1074/jbc.M104837200. PMID 11479302.
18. Cano E, Hazzalin CA, Kardalinou E, Buckle RS, Mahadevan LC (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 (11): 3599–609. PMID 8586671.
19. Girardin SE, 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.
20. 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. doi:10.1074/jbc.274.28.19949. PMID 10391943.
21. Slack DN, Seternes OM, Gabrielsen M, Keyse SM (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.
22. 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.
23. Wang T, Arifoglu P, Ronai Z, Tew KD (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.
24. Aguirre V, Werner ED, Giraud J, Lee YH, Shoelson SE, White MF (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.
25. Aguirre V, Uchida T, Yenush L, Davis R, White MF (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. doi:10.1074/jbc.275.12.9047. PMID 10722755.
26. Gao M, Labuda T, Xia Y, Gallagher E, Fang D, Liu YC, Karin M (October 2004). "Jun turnover is controlled through JNK-dependent phosphorylation of the E3 ligase Itch". Science. 306 (5694): 271–5. doi:10.1126/science.1099414. PMID 15358865.
27. Gallagher E, Gao M, Liu YC, Karin M (February 2006). "Activation of the E3 ubiquitin ligase Itch through a phosphorylation-induced conformational change". Proceedings of the National Academy of Sciences of the United States of America. 103 (6): 1717–22. doi:10.1073/pnas.0510664103. PMC 1413664. PMID 16446428.
28. 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. doi:10.1128/mcb.20.7.2334-2342.2000. PMC 85399. PMID 10713157.
29. Lee CM, Onésime D, Reddy CD, Dhanasekaran N, Reddy EP (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.
30. Park HS, Kim MS, Huh SH, Park J, Chung J, Kang SS, Choi EJ (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.
31. Xu S, Cobb MH (December 1997). "MEKK1 binds directly to the c-Jun N-terminal kinases/stress-activated protein kinases". J. Biol. Chem. 272 (51): 32056–60. doi:10.1074/jbc.272.51.32056. PMID 9405400.
32. Elion EA (September 1998). "Routing MAP kinase cascades". Science. 281 (5383): 1625–6. doi:10.1126/science.281.5383.1625. PMID 9767029. S2CID 28868990.
33. Cai Y, Lechner MS, Nihalani D, Prindle MJ, Holzman LB, Dressler GR (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.
34. Ito M, Yoshioka K, Akechi M, Yamashita S, Takamatsu N, Sugiyama K, Hibi M, Nakabeppu Y, Shiba T, Yamamoto KI (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. doi:10.1128/mcb.19.11.7539. PMC 84763. PMID 10523642.
35. Kelkar N, Gupta S, Dickens M, Davis RJ (February 2000). "Interaction of a mitogen-activated protein kinase signaling module with the neuronal protein JIP3". Mol. Cell. Biol. 20 (3): 1030–43. doi:10.1128/mcb.20.3.1030-1043.2000. PMC 85220. PMID 10629060.
36. 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. doi:10.1074/jbc.274.46.32580. PMID 10551811.
37. Wiltshire C, Matsushita M, Tsukada S, Gillespie DA, May GH (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.
38. 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

• Lin, A (2006). "The JNK Signaling Pathway (Molecular Biology Intelligence Unit)". Landes Bioscience. 1: 1–97. ISBN 978-1587061202.
• Davis RJ (2000). "Signal transduction by the JNK group of MAP kinases". Cell. 103 (2): 239–52. doi:10.1016/S0092-8674(00)00116-1. PMID 11057897. S2CID 343677.
• Liu J, Lin A (2007). "Wiring the cell signaling circuitry by the NF-kappa B and JNK1 crosstalk and its applications in human diseases". Oncogene. 26 (22): 3267–78. doi:10.1038/sj.onc.1210417. PMID 17496921. S2CID 28428831.

External links

• MAP Kinase Resource .

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