Skip to main content
PMC home page
Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 2004 Nov;63(Suppl 2):ii62–ii64. doi: 10.1136/ard.2004.028274

Mitogen activated protein kinases as targets for development of novel anti-inflammatory drugs

M Karin
PMCID: PMC1766783  PMID: 15479874

Full Text

The Full Text of this article is available as a PDF (53.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Angel P., Karin M. The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochim Biophys Acta. 1991 Dec 10;1072(2-3):129–157. doi: 10.1016/0304-419x(91)90011-9. [DOI] [PubMed] [Google Scholar]
  2. Barnes P. J., Karin M. Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med. 1997 Apr 10;336(15):1066–1071. doi: 10.1056/NEJM199704103361506. [DOI] [PubMed] [Google Scholar]
  3. Bonizzi Giuseppina, Karin Michael. The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends Immunol. 2004 Jun;25(6):280–288. doi: 10.1016/j.it.2004.03.008. [DOI] [PubMed] [Google Scholar]
  4. Brenner D. A., O'Hara M., Angel P., Chojkier M., Karin M. Prolonged activation of jun and collagenase genes by tumour necrosis factor-alpha. Nature. 1989 Feb 16;337(6208):661–663. doi: 10.1038/337661a0. [DOI] [PubMed] [Google Scholar]
  5. Cavigelli M., Li W. W., Lin A., Su B., Yoshioka K., Karin M. The tumor promoter arsenite stimulates AP-1 activity by inhibiting a JNK phosphatase. EMBO J. 1996 Nov 15;15(22):6269–6279. [PMC free article] [PubMed] [Google Scholar]
  6. Cerretti D. P., Kozlosky C. J., Mosley B., Nelson N., Van Ness K., Greenstreet T. A., March C. J., Kronheim S. R., Druck T., Cannizzaro L. A. Molecular cloning of the interleukin-1 beta converting enzyme. Science. 1992 Apr 3;256(5053):97–100. doi: 10.1126/science.1373520. [DOI] [PubMed] [Google Scholar]
  7. Chang L., Karin M. Mammalian MAP kinase signalling cascades. Nature. 2001 Mar 1;410(6824):37–40. doi: 10.1038/35065000. [DOI] [PubMed] [Google Scholar]
  8. Chang Lufen, Jones Ying, Ellisman Mark H., Goldstein Lawrence S. B., Karin Michael. JNK1 is required for maintenance of neuronal microtubules and controls phosphorylation of microtubule-associated proteins. Dev Cell. 2003 Apr;4(4):521–533. doi: 10.1016/s1534-5807(03)00094-7. [DOI] [PubMed] [Google Scholar]
  9. Chen Lee-Wei, Egan Laurence, Li Zhi-Wei, Greten Florian R., Kagnoff Martin F., Karin Michael. The two faces of IKK and NF-kappaB inhibition: prevention of systemic inflammation but increased local injury following intestinal ischemia-reperfusion. Nat Med. 2003 Apr 7;9(5):575–581. doi: 10.1038/nm849. [DOI] [PubMed] [Google Scholar]
  10. Dudley D. T., Pang L., Decker S. J., Bridges A. J., Saltiel A. R. A synthetic inhibitor of the mitogen-activated protein kinase cascade. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7686–7689. doi: 10.1073/pnas.92.17.7686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Favata M. F., Horiuchi K. Y., Manos E. J., Daulerio A. J., Stradley D. A., Feeser W. S., Van Dyk D. E., Pitts W. J., Earl R. A., Hobbs F. Identification of a novel inhibitor of mitogen-activated protein kinase kinase. J Biol Chem. 1998 Jul 17;273(29):18623–18632. doi: 10.1074/jbc.273.29.18623. [DOI] [PubMed] [Google Scholar]
  12. Freshney N. W., Rawlinson L., Guesdon F., Jones E., Cowley S., Hsuan J., Saklatvala J. Interleukin-1 activates a novel protein kinase cascade that results in the phosphorylation of Hsp27. Cell. 1994 Sep 23;78(6):1039–1049. doi: 10.1016/0092-8674(94)90278-x. [DOI] [PubMed] [Google Scholar]
  13. Ghosh Sankar, Karin Michael. Missing pieces in the NF-kappaB puzzle. Cell. 2002 Apr;109 (Suppl):S81–S96. doi: 10.1016/s0092-8674(02)00703-1. [DOI] [PubMed] [Google Scholar]
  14. Gupta S., Campbell D., Dérijard B., Davis R. J. Transcription factor ATF2 regulation by the JNK signal transduction pathway. Science. 1995 Jan 20;267(5196):389–393. doi: 10.1126/science.7824938. [DOI] [PubMed] [Google Scholar]
  15. Han J., Lee J. D., Bibbs L., Ulevitch R. J. A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science. 1994 Aug 5;265(5173):808–811. doi: 10.1126/science.7914033. [DOI] [PubMed] [Google Scholar]
  16. Han Z., Boyle D. L., Chang L., Bennett B., Karin M., Yang L., Manning A. M., Firestein G. S. c-Jun N-terminal kinase is required for metalloproteinase expression and joint destruction in inflammatory arthritis. J Clin Invest. 2001 Jul;108(1):73–81. doi: 10.1172/JCI12466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hibi M., Lin A., Smeal T., Minden A., Karin M. Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain. Genes Dev. 1993 Nov;7(11):2135–2148. doi: 10.1101/gad.7.11.2135. [DOI] [PubMed] [Google Scholar]
  18. Hirosumi Jiro, Tuncman Gürol, Chang Lufen, Görgün Cem Z., Uysal K. Teoman, Maeda Kazuhisa, Karin Michael, Hotamisligil Gökhan S. A central role for JNK in obesity and insulin resistance. Nature. 2002 Nov 21;420(6913):333–336. doi: 10.1038/nature01137. [DOI] [PubMed] [Google Scholar]
  19. Hsu Li-Chung, Park Jin Mo, Zhang Kezhong, Luo Jun-Li, Maeda Shin, Kaufman Randal J., Eckmann Lars, Guiney Donald G., Karin Michael. The protein kinase PKR is required for macrophage apoptosis after activation of Toll-like receptor 4. Nature. 2004 Mar 18;428(6980):341–345. doi: 10.1038/nature02405. [DOI] [PubMed] [Google Scholar]
  20. Karin M. The regulation of AP-1 activity by mitogen-activated protein kinases. J Biol Chem. 1995 Jul 14;270(28):16483–16486. doi: 10.1074/jbc.270.28.16483. [DOI] [PubMed] [Google Scholar]
  21. Karin Michael, Lin Anning. NF-kappaB at the crossroads of life and death. Nat Immunol. 2002 Mar;3(3):221–227. doi: 10.1038/ni0302-221. [DOI] [PubMed] [Google Scholar]
  22. Lee J. C., Laydon J. T., McDonnell P. C., Gallagher T. F., Kumar S., Green D., McNulty D., Blumenthal M. J., Heys J. R., Landvatter S. W. A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature. 1994 Dec 22;372(6508):739–746. doi: 10.1038/372739a0. [DOI] [PubMed] [Google Scholar]
  23. Li Qiutang, Verma Inder M. NF-kappaB regulation in the immune system. Nat Rev Immunol. 2002 Oct;2(10):725–734. doi: 10.1038/nri910. [DOI] [PubMed] [Google Scholar]
  24. Maeda Shin, Chang Lufen, Li Zhi-Wei, Luo Jun-Li, Leffert Hyam, Karin Michael. IKKbeta is required for prevention of apoptosis mediated by cell-bound but not by circulating TNFalpha. Immunity. 2003 Nov;19(5):725–737. doi: 10.1016/s1074-7613(03)00301-7. [DOI] [PubMed] [Google Scholar]
  25. McIntyre Kim W., Shuster David J., Gillooly Kathleen M., Dambach Donna M., Pattoli Mark A., Lu Pin, Zhou Xia-Di, Qiu Yuping, Zusi F. Christopher, Burke James R. A highly selective inhibitor of I kappa B kinase, BMS-345541, blocks both joint inflammation and destruction in collagen-induced arthritis in mice. Arthritis Rheum. 2003 Sep;48(9):2652–2659. doi: 10.1002/art.11131. [DOI] [PubMed] [Google Scholar]
  26. Medzhitov R. Toll-like receptors and innate immunity. Nat Rev Immunol. 2001 Nov;1(2):135–145. doi: 10.1038/35100529. [DOI] [PubMed] [Google Scholar]
  27. Nishikawa Masataka, Myoui Akira, Tomita Tetsuya, Takahi Koichiro, Nampei Akihide, Yoshikawa Hideki. Prevention of the onset and progression of collagen-induced arthritis in rats by the potent p38 mitogen-activated protein kinase inhibitor FR167653. Arthritis Rheum. 2003 Sep;48(9):2670–2681. doi: 10.1002/art.11227. [DOI] [PubMed] [Google Scholar]
  28. Park Jin Mo, Greten Florian R., Li Zhi-Wei, Karin Michael. Macrophage apoptosis by anthrax lethal factor through p38 MAP kinase inhibition. Science. 2002 Aug 29;297(5589):2048–2051. doi: 10.1126/science.1073163. [DOI] [PubMed] [Google Scholar]
  29. Senftleben U., Cao Y., Xiao G., Greten F. R., Krähn G., Bonizzi G., Chen Y., Hu Y., Fong A., Sun S. C. Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway. Science. 2001 Aug 24;293(5534):1495–1499. doi: 10.1126/science.1062677. [DOI] [PubMed] [Google Scholar]
  30. Thanos D., Maniatis T. Virus induction of human IFN beta gene expression requires the assembly of an enhanceosome. Cell. 1995 Dec 29;83(7):1091–1100. doi: 10.1016/0092-8674(95)90136-1. [DOI] [PubMed] [Google Scholar]
  31. Thornberry N. A., Bull H. G., Calaycay J. R., Chapman K. T., Howard A. D., Kostura M. J., Miller D. K., Molineaux S. M., Weidner J. R., Aunins J. A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Nature. 1992 Apr 30;356(6372):768–774. doi: 10.1038/356768a0. [DOI] [PubMed] [Google Scholar]
  32. Yuan J., Shaham S., Ledoux S., Ellis H. M., Horvitz H. R. The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme. Cell. 1993 Nov 19;75(4):641–652. doi: 10.1016/0092-8674(93)90485-9. [DOI] [PubMed] [Google Scholar]
  33. Zhang Lin, Wang Wei, Hayashi Yasuhito, Jester James V., Birk David E., Gao Min, Liu Chia-Yang, Kao Winston W-Y, Karin Michael, Xia Ying. A role for MEK kinase 1 in TGF-beta/activin-induced epithelium movement and embryonic eyelid closure. EMBO J. 2003 Sep 1;22(17):4443–4454. doi: 10.1093/emboj/cdg440. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Publishing Group

RESOURCES