A quantitative RNAi screen for JNK modifiers identifies Pvr as a novel regulator of Drosophila immune signaling.

Drosophila melanogaster responds to gram-negative bacterial challenges through the IMD pathway, a signal transduction cassette that is driven by the coordinated activities of JNK, NF-kappaB and caspase modules. While many modifiers of NF-kappaB activity were identified in cell culture and in vivo as...

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Autores principales:	David Bond, Edan Foley
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/3d533acb0c7646e8980f4a5ec7a50e1b
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spelling	oai:doaj.org-article:3d533acb0c7646e8980f4a5ec7a50e1b2021-11-25T05:48:31ZA quantitative RNAi screen for JNK modifiers identifies Pvr as a novel regulator of Drosophila immune signaling.1553-73661553-737410.1371/journal.ppat.1000655https://doaj.org/article/3d533acb0c7646e8980f4a5ec7a50e1b2009-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19893628/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Drosophila melanogaster responds to gram-negative bacterial challenges through the IMD pathway, a signal transduction cassette that is driven by the coordinated activities of JNK, NF-kappaB and caspase modules. While many modifiers of NF-kappaB activity were identified in cell culture and in vivo assays, the regulatory apparatus that determines JNK inputs into the IMD pathway is relatively unexplored. In this manuscript, we present the first quantitative screen of the entire genome of Drosophila for novel regulators of JNK activity in the IMD pathway. We identified a large number of gene products that negatively or positively impact on JNK activation in the IMD pathway. In particular, we identified the Pvr receptor tyrosine kinase as a potent inhibitor of JNK activation. In a series of in vivo and cell culture assays, we demonstrated that activation of the IMD pathway drives JNK-dependent expression of the Pvr ligands, Pvf2 and Pvf3, which in turn act through the Pvr/ERK MAP kinase pathway to attenuate the JNK and NF-kappaB arms of the IMD pathway. Our data illuminate a poorly understood arm of a critical and evolutionarily conserved innate immune response. Furthermore, given the pleiotropic involvement of JNK in eukaryotic cell biology, we believe that many of the novel regulators identified in this screen are of interest beyond immune signaling.David BondEdan FoleyPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 5, Iss 11, p e1000655 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 David Bond Edan Foley A quantitative RNAi screen for JNK modifiers identifies Pvr as a novel regulator of Drosophila immune signaling.
description	Drosophila melanogaster responds to gram-negative bacterial challenges through the IMD pathway, a signal transduction cassette that is driven by the coordinated activities of JNK, NF-kappaB and caspase modules. While many modifiers of NF-kappaB activity were identified in cell culture and in vivo assays, the regulatory apparatus that determines JNK inputs into the IMD pathway is relatively unexplored. In this manuscript, we present the first quantitative screen of the entire genome of Drosophila for novel regulators of JNK activity in the IMD pathway. We identified a large number of gene products that negatively or positively impact on JNK activation in the IMD pathway. In particular, we identified the Pvr receptor tyrosine kinase as a potent inhibitor of JNK activation. In a series of in vivo and cell culture assays, we demonstrated that activation of the IMD pathway drives JNK-dependent expression of the Pvr ligands, Pvf2 and Pvf3, which in turn act through the Pvr/ERK MAP kinase pathway to attenuate the JNK and NF-kappaB arms of the IMD pathway. Our data illuminate a poorly understood arm of a critical and evolutionarily conserved innate immune response. Furthermore, given the pleiotropic involvement of JNK in eukaryotic cell biology, we believe that many of the novel regulators identified in this screen are of interest beyond immune signaling.
format	article
author	David Bond Edan Foley
author_facet	David Bond Edan Foley
author_sort	David Bond
title	A quantitative RNAi screen for JNK modifiers identifies Pvr as a novel regulator of Drosophila immune signaling.
title_short	A quantitative RNAi screen for JNK modifiers identifies Pvr as a novel regulator of Drosophila immune signaling.
title_full	A quantitative RNAi screen for JNK modifiers identifies Pvr as a novel regulator of Drosophila immune signaling.
title_fullStr	A quantitative RNAi screen for JNK modifiers identifies Pvr as a novel regulator of Drosophila immune signaling.
title_full_unstemmed	A quantitative RNAi screen for JNK modifiers identifies Pvr as a novel regulator of Drosophila immune signaling.
title_sort	quantitative rnai screen for jnk modifiers identifies pvr as a novel regulator of drosophila immune signaling.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/3d533acb0c7646e8980f4a5ec7a50e1b
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A quantitative RNAi screen for JNK modifiers identifies Pvr as a novel regulator of Drosophila immune signaling.

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