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词条 MAPK8
释义

  1. Function

  2. Interactions

  3. References

  4. Further reading

  5. External links

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

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.[3]

Interactions

MAPK8 has been shown to interact with:

{{div col|colwidth=20em}}
  • Activating transcription factor 2,[4][5][6][7]
  • C-jun,[1][7][10][8][9][10][11][12]
  • CRK,[13]
  • DUSP10,[14]
  • DUSP1,[15]
  • DUSP22,[16]
  • GSTP1,[17]
  • IRS1,[18][19]
  • MAP2K4,[6][7][25][20][21]
  • MAP2K7,[7][22]
  • MAP3K1[23]
  • MAP3K2,[22]
  • MAPK8IP1,[24][25]
  • MAPK8IP3,[26][27]
  • Myc,[28]
  • REL,[29]
  • SH3BP5,[30] and
  • SPIB.[31]
{{Div col end}}

References

1. ^1 {{cite journal | vauthors = Dérijard B, Hibi M, Wu IH, Barrett T, Su B, Deng T, Karin M, Davis RJ | title = JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain | journal = Cell | volume = 76 | issue = 6 | pages = 1025–37 | date = April 1994 | pmid = 8137421 | pmc = | doi = 10.1016/0092-8674(94)90380-8 }}
2. ^{{cite journal | vauthors = Gupta S, Barrett T, Whitmarsh AJ, Cavanagh J, Sluss HK, Dérijard B, Davis RJ | title = Selective interaction of JNK protein kinase isoforms with transcription factors | journal = EMBO J. | volume = 15 | issue = 11 | pages = 2760–70 | date = July 1996 | pmid = 8654373 | pmc = 450211 | doi = }}
3. ^{{cite web | title = Entrez Gene: MAPK8 mitogen-activated protein kinase 8| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5599| accessdate = }}
4. ^{{cite journal | vauthors = Raingeaud J, Gupta S, Rogers JS, Dickens M, Han J, Ulevitch RJ, Davis RJ | title = Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine | journal = J. Biol. Chem. | volume = 270 | issue = 13 | pages = 7420–6 | date = March 1995 | pmid = 7535770 | doi = 10.1074/jbc.270.13.7420}}
5. ^{{cite journal | vauthors = Fuchs SY, Xie B, Adler V, Fried VA, Davis RJ, Ronai Z | title = c-Jun NH2-terminal kinases target the ubiquitination of their associated transcription factors | journal = J. Biol. Chem. | volume = 272 | issue = 51 | pages = 32163–8 | date = December 1997 | pmid = 9405416 | doi = 10.1074/jbc.272.51.32163}}
6. ^1 {{cite journal | vauthors = Chen Z, Cobb MH | title = Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2 | journal = J. Biol. Chem. | volume = 276 | issue = 19 | pages = 16070–5 | date = May 2001 | pmid = 11279118 | doi = 10.1074/jbc.M100681200 }}
7. ^1 2 3 {{cite journal | vauthors = Tournier C, Whitmarsh AJ, Cavanagh J, Barrett T, Davis RJ | title = Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 94 | issue = 14 | pages = 7337–42 | date = July 1997 | pmid = 9207092 | pmc = 23822 | doi = 10.1073/pnas.94.14.7337}}
8. ^{{cite journal | vauthors = Ishitani T, Takaesu G, Ninomiya-Tsuji J, Shibuya H, Gaynor RB, Matsumoto K | title = Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling | journal = EMBO J. | volume = 22 | issue = 23 | pages = 6277–88 | date = December 2003 | pmid = 14633987 | pmc = 291846 | doi = 10.1093/emboj/cdg605 }}
9. ^{{cite journal | vauthors = Nishitoh H, Saitoh M, Mochida Y, Takeda K, Nakano H, Rothe M, Miyazono K, Ichijo H | title = ASK1 is essential for JNK/SAPK activation by TRAF2 | journal = Mol. Cell | volume = 2 | issue = 3 | pages = 389–95 | date = September 1998 | pmid = 9774977 | doi = 10.1016/s1097-2765(00)80283-x}}
10. ^{{cite journal | vauthors = Yazgan O, Pfarr CM | title = Regulation of two JunD isoforms by Jun N-terminal kinases | journal = J. Biol. Chem. | volume = 277 | issue = 33 | pages = 29710–8 | date = August 2002 | pmid = 12052834 | doi = 10.1074/jbc.M204552200 }}
11. ^{{cite journal | vauthors = Tada K, Okazaki T, Sakon S, Kobarai T, Kurosawa K, Yamaoka S, Hashimoto H, Mak TW, Yagita H, Okumura K, Yeh WC, Nakano H | title = Critical roles of TRAF2 and TRAF5 in tumor necrosis factor-induced NF-kappa B activation and protection from cell death | journal = J. Biol. Chem. | volume = 276 | issue = 39 | pages = 36530–4 | date = September 2001 | pmid = 11479302 | doi = 10.1074/jbc.M104837200 }}
12. ^{{cite journal | vauthors = Cano E, Hazzalin CA, Kardalinou E, Buckle RS, Mahadevan LC | title = Neither ERK nor JNK/SAPK MAP kinase subtypes are essential for histone H3/HMG-14 phosphorylation or c-fos and c-jun induction | journal = J. Cell Sci. | volume = 108 | issue = 11| pages = 3599–609 | date = November 1995 | pmid = 8586671 | doi = }}
13. ^{{cite journal | vauthors = Girardin SE, Yaniv M | title = A direct interaction between JNK1 and CrkII is critical for Rac1-induced JNK activation | journal = EMBO J. | volume = 20 | issue = 13 | pages = 3437–46 | date = July 2001 | pmid = 11432831 | pmc = 125507 | doi = 10.1093/emboj/20.13.3437 }}
14. ^{{cite journal | vauthors = Tanoue T, Moriguchi T, Nishida E | title = Molecular cloning and characterization of a novel dual specificity phosphatase, MKP-5 | journal = J. Biol. Chem. | volume = 274 | issue = 28 | pages = 19949–56 | date = July 1999 | pmid = 10391943 | doi = 10.1074/jbc.274.28.19949}}
15. ^{{cite journal | vauthors = Slack DN, Seternes OM, Gabrielsen M, Keyse SM | title = Distinct binding determinants for ERK2/p38alpha and JNK map kinases mediate catalytic activation and substrate selectivity of map kinase phosphatase-1 | journal = J. Biol. Chem. | volume = 276 | issue = 19 | pages = 16491–500 | date = May 2001 | pmid = 11278799 | doi = 10.1074/jbc.M010966200 }}
16. ^{{cite journal | vauthors = Aoyama K, Nagata M, Oshima K, Matsuda T, Aoki N | title = Molecular cloning and characterization of a novel dual specificity phosphatase, LMW-DSP2, that lacks the cdc25 homology domain | journal = J. Biol. Chem. | volume = 276 | issue = 29 | pages = 27575–83 | date = July 2001 | pmid = 11346645 | doi = 10.1074/jbc.M100408200 | pmc = 3757226 }}
17. ^{{cite journal | vauthors = Wang T, Arifoglu P, Ronai Z, Tew KD | title = Glutathione S-transferase P1-1 (GSTP1-1) inhibits c-Jun N-terminal kinase (JNK1) signaling through interaction with the C terminus | journal = J. Biol. Chem. | volume = 276 | issue = 24 | pages = 20999–1003 | date = June 2001 | pmid = 11279197 | doi = 10.1074/jbc.M101355200 }}
18. ^{{cite journal | vauthors = Aguirre V, Werner ED, Giraud J, Lee YH, Shoelson SE, White MF | title = Phosphorylation of Ser307 in insulin receptor substrate-1 blocks interactions with the insulin receptor and inhibits insulin action | journal = J. Biol. Chem. | volume = 277 | issue = 2 | pages = 1531–7 | date = January 2002 | pmid = 11606564 | doi = 10.1074/jbc.M101521200 }}
19. ^{{cite journal | vauthors = Aguirre V, Uchida T, Yenush L, Davis R, White MF | title = The c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307) | journal = J. Biol. Chem. | volume = 275 | issue = 12 | pages = 9047–54 | date = March 2000 | pmid = 10722755 | doi = 10.1074/jbc.275.12.9047}}
20. ^{{cite journal | vauthors = Lee CM, Onésime D, Reddy CD, Dhanasekaran N, Reddy EP | title = JLP: A scaffolding protein that tethers JNK/p38MAPK signaling modules and transcription factors | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 99 | issue = 22 | pages = 14189–94 | date = October 2002 | pmid = 12391307 | pmc = 137859 | doi = 10.1073/pnas.232310199 }}
21. ^{{cite journal | vauthors = Park HS, Kim MS, Huh SH, Park J, Chung J, Kang SS, Choi EJ | title = Akt (protein kinase B) negatively regulates SEK1 by means of protein phosphorylation | journal = J. Biol. Chem. | volume = 277 | issue = 4 | pages = 2573–8 | date = January 2002 | pmid = 11707464 | doi = 10.1074/jbc.M110299200 }}
22. ^1 2 {{cite journal | vauthors = Cheng J, Yang J, Xia Y, Karin M, Su B | title = Synergistic interaction of MEK kinase 2, c-Jun N-terminal kinase (JNK) kinase 2, and JNK1 results in efficient and specific JNK1 activation | journal = Mol. Cell. Biol. | volume = 20 | issue = 7 | pages = 2334–42 | date = April 2000 | pmid = 10713157 | pmc = 85399 | doi = 10.1128/mcb.20.7.2334-2342.2000}}
23. ^{{cite journal | vauthors = Xu S, Cobb MH | title = MEKK1 binds directly to the c-Jun N-terminal kinases/stress-activated protein kinases | journal = J. Biol. Chem. | volume = 272 | issue = 51 | pages = 32056–60 | date = December 1997 | pmid = 9405400 | doi = 10.1074/jbc.272.51.32056}}
24. ^{{cite journal | vauthors = Elion EA | title = Routing MAP kinase cascades | journal = Science | volume = 281 | issue = 5383 | pages = 1625–6 | date = September 1998 | pmid = 9767029 | doi = 10.1126/science.281.5383.1625}}
25. ^{{cite journal | vauthors = Cai Y, Lechner MS, Nihalani D, Prindle MJ, Holzman LB, Dressler GR | title = Phosphorylation of Pax2 by the c-Jun N-terminal kinase and enhanced Pax2-dependent transcription activation | journal = J. Biol. Chem. | volume = 277 | issue = 2 | pages = 1217–22 | date = January 2002 | pmid = 11700324 | doi = 10.1074/jbc.M109663200 }}
26. ^{{cite journal | vauthors = Ito M, Yoshioka K, Akechi M, Yamashita S, Takamatsu N, Sugiyama K, Hibi M, Nakabeppu Y, Shiba T, Yamamoto KI | title = JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a Scaffold factor in the JNK signaling pathway | journal = Mol. Cell. Biol. | volume = 19 | issue = 11 | pages = 7539–48 | date = November 1999 | pmid = 10523642 | pmc = 84763 | doi = 10.1128/mcb.19.11.7539}}
27. ^{{cite journal | vauthors = Kelkar N, Gupta S, Dickens M, Davis RJ | title = Interaction of a mitogen-activated protein kinase signaling module with the neuronal protein JIP3 | journal = Mol. Cell. Biol. | volume = 20 | issue = 3 | pages = 1030–43 | date = February 2000 | pmid = 10629060 | pmc = 85220 | doi = 10.1128/mcb.20.3.1030-1043.2000}}
28. ^{{cite journal | vauthors = Noguchi K, Kitanaka C, Yamana H, Kokubu A, Mochizuki T, Kuchino Y | title = Regulation of c-Myc through phosphorylation at Ser-62 and Ser-71 by c-Jun N-terminal kinase | journal = J. Biol. Chem. | volume = 274 | issue = 46 | pages = 32580–7 | date = November 1999 | pmid = 10551811 | doi = 10.1074/jbc.274.46.32580}}
29. ^1 {{cite journal | vauthors = Meyer CF, Wang X, Chang C, Templeton D, Tan TH | title = Interaction between c-Rel and the mitogen-activated protein kinase kinase kinase 1 signaling cascade in mediating kappaB enhancer activation | journal = J. Biol. Chem. | volume = 271 | issue = 15 | pages = 8971–6 | date = April 1996 | pmid = 8621542 | doi = 10.1074/jbc.271.15.8971}}
30. ^{{cite journal | vauthors = Wiltshire C, Matsushita M, Tsukada S, Gillespie DA, May GH | title = A new c-Jun N-terminal kinase (JNK)-interacting protein, Sab (SH3BP5), associates with mitochondria | journal = Biochem. J. | volume = 367 | issue = Pt 3 | pages = 577–85 | date = November 2002 | pmid = 12167088 | pmc = 1222945 | doi = 10.1042/BJ20020553 }}
31. ^{{cite journal | vauthors = Mao C, Ray-Gallet D, Tavitian A, Moreau-Gachelin F | title = Differential phosphorylations of Spi-B and Spi-1 transcription factors | journal = Oncogene | volume = 12 | issue = 4 | pages = 863–73 | date = February 1996 | pmid = 8632909 | doi = }}

Further reading

{{refbegin | 2}}
  • {{cite journal | vauthors = Davis RJ | title = Signal transduction by the JNK group of MAP kinases | journal = Cell | volume = 103 | issue = 2 | pages = 239–52 | year = 2000 | pmid = 11057897 | doi = 10.1016/S0092-8674(00)00116-1 }}
  • {{cite journal | vauthors = Liu J, Lin A | title = Wiring the cell signaling circuitry by the NF-kappa B and JNK1 crosstalk and its applications in human diseases | journal = Oncogene | volume = 26 | issue = 22 | pages = 3267–78 | year = 2007 | pmid = 17496921 | doi = 10.1038/sj.onc.1210417 }}
{{refend}}

External links

  • MAP Kinase Resource.
{{NLM content}}{{PDB Gallery|geneid=5599}}{{Serine/threonine-specific protein kinases}}{{Enzymes}}{{Portal bar|Molecular and Cellular Biology|border=no}}

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