A novel mechanism of JNK1 activation. Nuclear translocation and activation of JNK1 during ischemia and reperfusion - PubMed

Affiliations

• PMID: 9195981
• DOI: 10.1074/jbc.272.26.16657

Free article

A novel mechanism of JNK1 activation. Nuclear translocation and activation of JNK1 during ischemia and reperfusion

Y Mizukami et al. J Biol Chem. 1997.

Free article

Abstract

Cytokines and various cellular stresses are known to activate c-Jun NH2-terminal kinase (JNK), which plays a role in conveying signals from the cytosol to the nucleus. Here we investigate the translocation and activation of JNK1 during ischemia and reperfusion in perfused rat heart. Ischemia induces the translocation of JNK1 from the cytosol fraction to the nuclear fraction in a time-dependent manner. Immunohistochemical observation also shows that JNK1 staining in the nucleus is enhanced after ischemia. During reperfusion after ischemia, further nuclear translocation of JNK1 is apparently inhibited. In contrast, JNK1 activity in the nuclear fraction does not increased during ischemia but increases significantly during reperfusion with a peak at 10 min of reperfusion. The activation of JNK1 is confirmed by the phosphorylation of endogenous c-Jun (Ser-73) with similar kinetics. The level of c-jun mRNA also increases during reperfusion but not during ischemia. Based on fractionation and immunohistochemical analyses, an upstream kinase for JNK1, SAPK/ERK kinase 1 (SEK1), is constantly present in both the nucleus and cytoplasm throughout ischemia and reperfusion, whereas an upstream kinase for mitogen-activated protein kinase, MAPK/ERK kinase 1, remains in the cytosol. Furthermore, phosphorylation at Thr-223 of SEK1, necessary for its activation, rapidly increases in the nuclear fraction during postischemic reperfusion. These findings demonstrate that JNK1 translocates to the nucleus during ischemia without activation and is then activated during reperfusion, probably by SEK1 in the nucleus.

Similar articles

• Mitogen-activated protein kinase translocates to the nucleus during ischaemia and is activated during reperfusion.

  Mizukami Y, Yoshida Ki. Mizukami Y, et al. Biochem J. 1997 May 1;323 ( Pt 3)(Pt 3):785-90. doi: 10.1042/bj3230785. Biochem J. 1997. PMID: 9169613 Free PMC article.

• Stimulation of the stress-activated mitogen-activated protein kinase subfamilies in perfused heart. p38/RK mitogen-activated protein kinases and c-Jun N-terminal kinases are activated by ischemia/reperfusion.

  Bogoyevitch MA, Gillespie-Brown J, Ketterman AJ, Fuller SJ, Ben-Levy R, Ashworth A, Marshall CJ, Sugden PH. Bogoyevitch MA, et al. Circ Res. 1996 Aug;79(2):162-73. doi: 10.1161/01.res.79.2.162. Circ Res. 1996. PMID: 8755992 Review.

• Stimulation of c-Jun kinase and mitogen-activated protein kinase by ischemia and reperfusion in the perfused rat heart.

  Knight RJ, Buxton DB. Knight RJ, et al. Biochem Biophys Res Commun. 1996 Jan 5;218(1):83-8. doi: 10.1006/bbrc.1996.0016. Biochem Biophys Res Commun. 1996. PMID: 8573181

• PKC-dependent activation of p44/p42 MAPKs during myocardial ischemia-reperfusion in conscious rabbits.

  Ping P, Zhang J, Cao X, Li RC, Kong D, Tang XL, Qiu Y, Manchikalapudi S, Auchampach JA, Black RG, Bolli R. Ping P, et al. Am J Physiol. 1999 May;276(5):H1468-81. doi: 10.1152/ajpheart.1999.276.5.H1468. Am J Physiol. 1999. PMID: 10330229

Cited by

• Role of Mitogen-Activated Protein Kinases in Myocardial Ischemia-Reperfusion Injury during Heart Transplantation.

  Vassalli G, Milano G, Moccetti T. Vassalli G, et al. J Transplant. 2012;2012:928954. doi: 10.1155/2012/928954. Epub 2012 Mar 18. J Transplant. 2012. PMID: 22530110 Free PMC article.

• Systematic discovery of in vivo phosphorylation networks.

  Linding R, Jensen LJ, Ostheimer GJ, van Vugt MA, Jørgensen C, Miron IM, Diella F, Colwill K, Taylor L, Elder K, Metalnikov P, Nguyen V, Pasculescu A, Jin J, Park JG, Samson LD, Woodgett JR, Russell RB, Bork P, Yaffe MB, Pawson T. Linding R, et al. Cell. 2007 Jun 29;129(7):1415-26. doi: 10.1016/j.cell.2007.05.052. Epub 2007 Jun 14. Cell. 2007. PMID: 17570479 Free PMC article.

• Glucocorticoids antagonize AP-1 by inhibiting the Activation/phosphorylation of JNK without affecting its subcellular distribution.

  González MV, Jiménez B, Berciano MT, González-Sancho JM, Caelles C, Lafarga M, Muñoz A. González MV, et al. J Cell Biol. 2000 Sep 4;150(5):1199-208. doi: 10.1083/jcb.150.5.1199. J Cell Biol. 2000. PMID: 10974006 Free PMC article.

• Downregulation of the Long Noncoding RNA IALNCR Targeting MAPK8/JNK1 Promotes Apoptosis and Antagonizes Bovine Viral Diarrhea Virus Replication in Host Cells.

  Gao X, Sun X, Yao X, Wang Y, Li Y, Jiang X, Han Y, Zhong L, Wang L, Song H, Xu Y. Gao X, et al. J Virol. 2022 Sep 14;96(17):e0111322. doi: 10.1128/jvi.01113-22. Epub 2022 Aug 22. J Virol. 2022. PMID: 35993735 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Molecular Biology Databases

  • PhosphoSitePlus

• Research Materials

  • NCI CPTC Antibody Characterization Program

• Miscellaneous

  • NCI CPTAC Assay Portal