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A Non-Redundant Role for Drosophila Mkk4 and Hemipterous/Mkk7 in TAK1-Mediated Activation of JNK
BACKGROUND: The JNK pathway is a mitogen-activated protein (MAP) kinase pathway involved in the regulation of numerous physiological processes during development and in response to environmental stress. JNK activity is controlled by two MAPK kinases (MAPKK), Mkk4 and Mkk7. Mkk7 plays a prominent rol...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2766050/ https://www.ncbi.nlm.nih.gov/pubmed/19888449 http://dx.doi.org/10.1371/journal.pone.0007709 |
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author | Geuking, Peter Narasimamurthy, Rajesh Lemaitre, Bruno Basler, Konrad Leulier, François |
author_facet | Geuking, Peter Narasimamurthy, Rajesh Lemaitre, Bruno Basler, Konrad Leulier, François |
author_sort | Geuking, Peter |
collection | PubMed |
description | BACKGROUND: The JNK pathway is a mitogen-activated protein (MAP) kinase pathway involved in the regulation of numerous physiological processes during development and in response to environmental stress. JNK activity is controlled by two MAPK kinases (MAPKK), Mkk4 and Mkk7. Mkk7 plays a prominent role upon Tumor Necrosis Factor (TNF) stimulation. Eiger, the unique TNF-superfamily ligand in Drosophila, potently activates JNK signaling through the activation of the MAPKKK Tak1. METHODOLOGY/PRINCIPAL FINDINGS: In a dominant suppressor screen for new components of the Eiger/JNK-pathway in Drosophila, we have identified an allelic series of the Mkk4 gene. Our genetic and biochemical results demonstrate that Mkk4 is dispensable for normal development and host resistance to systemic bacterial infection but plays a non-redundant role as a MAPKK acting in parallel to Hemipterous/Mkk7 in dTAK1-mediated JNK activation upon Eiger and Imd pathway activation. CONCLUSIONS/SIGNIFICANCE: In contrast to mammals, it seems that in Drosophila both MAPKKs, Hep/Mkk7 and Mkk4, are required to induce JNK upon TNF or pro-inflammatory stimulation. |
format | Text |
id | pubmed-2766050 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-27660502009-11-04 A Non-Redundant Role for Drosophila Mkk4 and Hemipterous/Mkk7 in TAK1-Mediated Activation of JNK Geuking, Peter Narasimamurthy, Rajesh Lemaitre, Bruno Basler, Konrad Leulier, François PLoS One Research Article BACKGROUND: The JNK pathway is a mitogen-activated protein (MAP) kinase pathway involved in the regulation of numerous physiological processes during development and in response to environmental stress. JNK activity is controlled by two MAPK kinases (MAPKK), Mkk4 and Mkk7. Mkk7 plays a prominent role upon Tumor Necrosis Factor (TNF) stimulation. Eiger, the unique TNF-superfamily ligand in Drosophila, potently activates JNK signaling through the activation of the MAPKKK Tak1. METHODOLOGY/PRINCIPAL FINDINGS: In a dominant suppressor screen for new components of the Eiger/JNK-pathway in Drosophila, we have identified an allelic series of the Mkk4 gene. Our genetic and biochemical results demonstrate that Mkk4 is dispensable for normal development and host resistance to systemic bacterial infection but plays a non-redundant role as a MAPKK acting in parallel to Hemipterous/Mkk7 in dTAK1-mediated JNK activation upon Eiger and Imd pathway activation. CONCLUSIONS/SIGNIFICANCE: In contrast to mammals, it seems that in Drosophila both MAPKKs, Hep/Mkk7 and Mkk4, are required to induce JNK upon TNF or pro-inflammatory stimulation. Public Library of Science 2009-11-03 /pmc/articles/PMC2766050/ /pubmed/19888449 http://dx.doi.org/10.1371/journal.pone.0007709 Text en Geuking et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Geuking, Peter Narasimamurthy, Rajesh Lemaitre, Bruno Basler, Konrad Leulier, François A Non-Redundant Role for Drosophila Mkk4 and Hemipterous/Mkk7 in TAK1-Mediated Activation of JNK |
title | A Non-Redundant Role for Drosophila Mkk4 and Hemipterous/Mkk7 in TAK1-Mediated Activation of JNK |
title_full | A Non-Redundant Role for Drosophila Mkk4 and Hemipterous/Mkk7 in TAK1-Mediated Activation of JNK |
title_fullStr | A Non-Redundant Role for Drosophila Mkk4 and Hemipterous/Mkk7 in TAK1-Mediated Activation of JNK |
title_full_unstemmed | A Non-Redundant Role for Drosophila Mkk4 and Hemipterous/Mkk7 in TAK1-Mediated Activation of JNK |
title_short | A Non-Redundant Role for Drosophila Mkk4 and Hemipterous/Mkk7 in TAK1-Mediated Activation of JNK |
title_sort | non-redundant role for drosophila mkk4 and hemipterous/mkk7 in tak1-mediated activation of jnk |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2766050/ https://www.ncbi.nlm.nih.gov/pubmed/19888449 http://dx.doi.org/10.1371/journal.pone.0007709 |
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