7n8t

Structural highlights

Function

MK09_HUMAN Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK9/JNK2. In turn, MAPK9/JNK2 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. In response to oxidative or ribotoxic stresses, inhibits rRNA synthesis by phosphorylating and inactivating the RNA polymerase 1-specific transcription initiation factor RRN3. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including TP53 and YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Upon T-cell receptor (TCR) stimulation, is activated by CARMA1, BCL10, MAP2K7 and MAP3K7/TAK1 to regulate JUN protein levels. Plays an important role in the osmotic stress-induced epithelial tight-junctions disruption. When activated, promotes beta-catenin/CTNNB1 degradation and inhibits the canonical Wnt signaling pathway. Participates also in neurite growth in spiral ganglion neurons.^{[1] [2] [3] [4] [5] [6]} MAPK9 isoforms display different binding patterns: alpha-1 and alpha-2 preferentially bind to JUN, whereas beta-1 and beta-2 bind to ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms. JUNB is not a substrate for JNK2 alpha-2, and JUND binds only weakly to it.^{[7] [8] [9] [10] [11] [12]}

See Also

• Mitogen-activated protein kinase 3D structures

References

1. ↑ De Graeve F, Bahr A, Sabapathy KT, Hauss C, Wagner EF, Kedinger C, Chatton B. Role of the ATFa/JNK2 complex in Jun activation. Oncogene. 1999 Jun 10;18(23):3491-500. PMID:10376527 doi:http://dx.doi.org/10.1038/sj.onc.1202723
2. ↑ Mayer C, Bierhoff H, Grummt I. The nucleolus as a stress sensor: JNK2 inactivates the transcription factor TIF-IA and down-regulates rRNA synthesis. Genes Dev. 2005 Apr 15;19(8):933-41. Epub 2005 Apr 1. PMID:15805466 doi:http://dx.doi.org/10.1101/gad.333205
3. ↑ Oleinik NV, Krupenko NI, Krupenko SA. Cooperation between JNK1 and JNK2 in activation of p53 apoptotic pathway. Oncogene. 2007 Nov 8;26(51):7222-30. Epub 2007 May 21. PMID:17525747 doi:http://dx.doi.org/10.1038/sj.onc.1210526
4. ↑ Hu D, Bi X, Fang W, Han A, Yang W. GSK3beta is involved in JNK2-mediated beta-catenin inhibition. PLoS One. 2009 Aug 13;4(8):e6640. doi: 10.1371/journal.pone.0006640. PMID:19675674 doi:http://dx.doi.org/10.1371/journal.pone.0006640
5. ↑ Samak G, Suzuki T, Bhargava A, Rao RK. c-Jun NH2-terminal kinase-2 mediates osmotic stress-induced tight junction disruption in the intestinal epithelium. Am J Physiol Gastrointest Liver Physiol. 2010 Sep;299(3):G572-84. doi:, 10.1152/ajpgi.00265.2010. Epub 2010 Jul 1. PMID:20595622 doi:http://dx.doi.org/10.1152/ajpgi.00265.2010
6. ↑ Tomlinson V, Gudmundsdottir K, Luong P, Leung KY, Knebel A, Basu S. JNK phosphorylates Yes-associated protein (YAP) to regulate apoptosis. Cell Death Dis. 2010;1:e29. doi: 10.1038/cddis.2010.7. PMID:21364637 doi:10.1038/cddis.2010.7
7. ↑ De Graeve F, Bahr A, Sabapathy KT, Hauss C, Wagner EF, Kedinger C, Chatton B. Role of the ATFa/JNK2 complex in Jun activation. Oncogene. 1999 Jun 10;18(23):3491-500. PMID:10376527 doi:http://dx.doi.org/10.1038/sj.onc.1202723
8. ↑ Mayer C, Bierhoff H, Grummt I. The nucleolus as a stress sensor: JNK2 inactivates the transcription factor TIF-IA and down-regulates rRNA synthesis. Genes Dev. 2005 Apr 15;19(8):933-41. Epub 2005 Apr 1. PMID:15805466 doi:http://dx.doi.org/10.1101/gad.333205
9. ↑ Oleinik NV, Krupenko NI, Krupenko SA. Cooperation between JNK1 and JNK2 in activation of p53 apoptotic pathway. Oncogene. 2007 Nov 8;26(51):7222-30. Epub 2007 May 21. PMID:17525747 doi:http://dx.doi.org/10.1038/sj.onc.1210526
10. ↑ Hu D, Bi X, Fang W, Han A, Yang W. GSK3beta is involved in JNK2-mediated beta-catenin inhibition. PLoS One. 2009 Aug 13;4(8):e6640. doi: 10.1371/journal.pone.0006640. PMID:19675674 doi:http://dx.doi.org/10.1371/journal.pone.0006640
11. ↑ Samak G, Suzuki T, Bhargava A, Rao RK. c-Jun NH2-terminal kinase-2 mediates osmotic stress-induced tight junction disruption in the intestinal epithelium. Am J Physiol Gastrointest Liver Physiol. 2010 Sep;299(3):G572-84. doi:, 10.1152/ajpgi.00265.2010. Epub 2010 Jul 1. PMID:20595622 doi:http://dx.doi.org/10.1152/ajpgi.00265.2010
12. ↑ Tomlinson V, Gudmundsdottir K, Luong P, Leung KY, Knebel A, Basu S. JNK phosphorylates Yes-associated protein (YAP) to regulate apoptosis. Cell Death Dis. 2010;1:e29. doi: 10.1038/cddis.2010.7. PMID:21364637 doi:10.1038/cddis.2010.7