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The mitogen-activated protein kinase p38 regulates activator protein 1 by direct phosphorylation of c-Jun.
Int J Biochem Cell Biol. 2007; 39(12):2278-88.IJ

Abstract

The involvement of p38 in fundamental physiological processes and the fact that deregulation often leads to disease indicates the potential impact of p38 dependent mechanisms. Here we demonstrate a new pathway that includes the induction of the mitogen activated protein kinase p38 by protein kinase C and results in a specific phosphorylation of c-Jun in T-lymphocytes. P38 directly phosphorylates c-Jun within its transactivation domain at serine 63 and serine 73 and thus posttranscriptionally affects the presence of DNA-bound phosphorylated c-Jun, a prerequisite for activator protein 1 dependent gene transcription. Moreover, DNA-binding activity of c-Fos, FosB, and JunB were also dependent on the p38 protein kinase activity, whereas JunD, Fra-1 and Fra-2 were not affected. Although we show that stress induced mitogen activated protein kinases share c-Jun as a substrate for phosphorylation, p38 mediated effects could not be rescued by the c-Jun N-terminal kinases. This demonstrates that the protein kinase p38 plays a unique and non-redundant role in posttranslational c-Jun regulation. The induction of a p38 dependent c-Jun phosphorylation was comparable in both CD4(+) and CD8(+) T-cells, proposing a ubiquitous pathway that is not linked to T-cell subtype and effector function. In contrast, ATF-2 was predominantly phosphorylated in CD8(+) T-cells. Different cell lines show p38-dependent c-Jun phosphorylation upon phorbol ester induction but there is evidence that the simian virus 40 large T-antigen may interfere with this pathway.

Authors+Show Affiliations

Center for Clinical Research, Department of Anesthesiology, University Hospital Freiburg, Breisacherstrasse 66, D-79106 Freiburg, Germany. humar@ana1.ukl.uni-freiburg.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17689131

Citation

Humar, Matjaz, et al. "The Mitogen-activated Protein Kinase P38 Regulates Activator Protein 1 By Direct Phosphorylation of C-Jun." The International Journal of Biochemistry & Cell Biology, vol. 39, no. 12, 2007, pp. 2278-88.
Humar M, Loop T, Schmidt R, et al. The mitogen-activated protein kinase p38 regulates activator protein 1 by direct phosphorylation of c-Jun. Int J Biochem Cell Biol. 2007;39(12):2278-88.
Humar, M., Loop, T., Schmidt, R., Hoetzel, A., Roesslein, M., Andriopoulos, N., Pahl, H. L., Geiger, K. K., & Pannen, B. H. (2007). The mitogen-activated protein kinase p38 regulates activator protein 1 by direct phosphorylation of c-Jun. The International Journal of Biochemistry & Cell Biology, 39(12), 2278-88.
Humar M, et al. The Mitogen-activated Protein Kinase P38 Regulates Activator Protein 1 By Direct Phosphorylation of C-Jun. Int J Biochem Cell Biol. 2007;39(12):2278-88. PubMed PMID: 17689131.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The mitogen-activated protein kinase p38 regulates activator protein 1 by direct phosphorylation of c-Jun. AU - Humar,Matjaz, AU - Loop,Torsten, AU - Schmidt,Rene, AU - Hoetzel,Alexander, AU - Roesslein,Martin, AU - Andriopoulos,Nikolaos, AU - Pahl,Heike L, AU - Geiger,Klaus K, AU - Pannen,Benedikt H J, Y1 - 2007/07/01/ PY - 2007/04/11/received PY - 2007/06/27/revised PY - 2007/06/27/accepted PY - 2007/8/11/pubmed PY - 2008/1/4/medline PY - 2007/8/11/entrez SP - 2278 EP - 88 JF - The international journal of biochemistry & cell biology JO - Int J Biochem Cell Biol VL - 39 IS - 12 N2 - The involvement of p38 in fundamental physiological processes and the fact that deregulation often leads to disease indicates the potential impact of p38 dependent mechanisms. Here we demonstrate a new pathway that includes the induction of the mitogen activated protein kinase p38 by protein kinase C and results in a specific phosphorylation of c-Jun in T-lymphocytes. P38 directly phosphorylates c-Jun within its transactivation domain at serine 63 and serine 73 and thus posttranscriptionally affects the presence of DNA-bound phosphorylated c-Jun, a prerequisite for activator protein 1 dependent gene transcription. Moreover, DNA-binding activity of c-Fos, FosB, and JunB were also dependent on the p38 protein kinase activity, whereas JunD, Fra-1 and Fra-2 were not affected. Although we show that stress induced mitogen activated protein kinases share c-Jun as a substrate for phosphorylation, p38 mediated effects could not be rescued by the c-Jun N-terminal kinases. This demonstrates that the protein kinase p38 plays a unique and non-redundant role in posttranslational c-Jun regulation. The induction of a p38 dependent c-Jun phosphorylation was comparable in both CD4(+) and CD8(+) T-cells, proposing a ubiquitous pathway that is not linked to T-cell subtype and effector function. In contrast, ATF-2 was predominantly phosphorylated in CD8(+) T-cells. Different cell lines show p38-dependent c-Jun phosphorylation upon phorbol ester induction but there is evidence that the simian virus 40 large T-antigen may interfere with this pathway. SN - 1357-2725 UR - https://www.unboundmedicine.com/medline/citation/17689131/The_mitogen_activated_protein_kinase_p38_regulates_activator_protein_1_by_direct_phosphorylation_of_c_Jun_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1357-2725(07)00211-7 DB - PRIME DP - Unbound Medicine ER -