MAPK8

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 33,099,855 bp [2] End 33,169,115 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ganglionic eminence Achilles tendon stromal cell of endometrium islet of Langerhans internal globus pallidus gallbladder pons rectum prefrontal cortex cerebellar hemisphere Top expressed in secondary oocyte barrel cortex superior cervical ganglion ganglionic eminence visual cortex piriform cortex habenula medial dorsal nucleus primary motor cortex medial ganglionic eminence More reference expression data BioGPS 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 protein binding enzyme binding ATP binding JUN kinase activity kinase activity Cellular component cytosol nucleoplasm nucleus mitochondrion cytoplasm neuron projection axon basal dendrite Biological process phosphorylation rhythmic process response to stress negative regulation of apoptotic process negative regulation of protein binding 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 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 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: 33.1 – 33.17 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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

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.
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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.
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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. doi:10.1242/jcs.108.11.3599. 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. Bibcode:2004Sci...306..271G. doi: 10.1126/science.1099414 . PMID   15358865. S2CID   31876966.
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. Bibcode:2006PNAS..103.1717G. 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. Bibcode:2002PNAS...9914189L. 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.
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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 Archived 2021-04-15 at the Wayback Machine .

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