File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Fyn and p38 signaling are both required for maximal hypertonic activation of the osmotic response element-binding protein/tonicity-responsive enhancer-binding protein (OREBP/TonEBP)

TitleFyn and p38 signaling are both required for maximal hypertonic activation of the osmotic response element-binding protein/tonicity-responsive enhancer-binding protein (OREBP/TonEBP)
Authors
Issue Date2002
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal Of Biological Chemistry, 2002, v. 277 n. 48, p. 46085-46092 How to Cite?
AbstractWhen cells are challenged by hyperosmotic stress, one of the crucial adaptive responses is the expression of osmo-protective genes that are responsible for raising the intracellular level of compatible osmolytes such as sorbitol, betaine, and myo-inositol. This is achieved by the activation of the transcription factor called OREBP (also known as TonEBP or NFAT5) that specifically binds to the osmotic response element (ORE) or tonicity-responsive enhancer that enhances the transcription of these genes. Here we show that p38, a subgroup of the mitogen-activated kinases activated by hypertonic stress, and Fyn, a shrinkage-activated tyrosine kinase, are both involved in the hypertonic activation of OREBP/TonEBP. Inhibition of p38 by SB203580 or by the dominant negative p38 mutant partially blocked the hypertonic induction of ORE reporter (reporter gene regulated by ORE). Similarly, hypertonic activation of ORE reporter was partially blocked by pharmacological inhibition of Fyn or by a dominant negative Fyn and was attenuated in Fyn-deficient cells. Importantly, inhibiting p38 in Fyn-deficient cells almost completely abolished the hypertonic induction of ORE reporter activity, indicating that p38 and Fyn are the major signaling pathways for the hypertonic activation of OREBP/TonEBP. Further we show that the transactivation domain of OREBP/TonEBP is the target of p38- and Fyn-mediated hypertonic activation. These results indicate a dual control in regulating the expression of the osmoprotective genes in mammalian cells.
Persistent Identifierhttp://hdl.handle.net/10722/88036
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorKo, BCBen_HK
dc.contributor.authorLam, AKMen_HK
dc.contributor.authorKapus, Aen_HK
dc.contributor.authorFan, Len_HK
dc.contributor.authorChung, SKen_HK
dc.contributor.authorChung, SSMen_HK
dc.date.accessioned2010-09-06T09:37:49Z-
dc.date.available2010-09-06T09:37:49Z-
dc.date.issued2002en_HK
dc.identifier.citationJournal Of Biological Chemistry, 2002, v. 277 n. 48, p. 46085-46092en_HK
dc.identifier.issn0021-9258en_HK
dc.identifier.urihttp://hdl.handle.net/10722/88036-
dc.description.abstractWhen cells are challenged by hyperosmotic stress, one of the crucial adaptive responses is the expression of osmo-protective genes that are responsible for raising the intracellular level of compatible osmolytes such as sorbitol, betaine, and myo-inositol. This is achieved by the activation of the transcription factor called OREBP (also known as TonEBP or NFAT5) that specifically binds to the osmotic response element (ORE) or tonicity-responsive enhancer that enhances the transcription of these genes. Here we show that p38, a subgroup of the mitogen-activated kinases activated by hypertonic stress, and Fyn, a shrinkage-activated tyrosine kinase, are both involved in the hypertonic activation of OREBP/TonEBP. Inhibition of p38 by SB203580 or by the dominant negative p38 mutant partially blocked the hypertonic induction of ORE reporter (reporter gene regulated by ORE). Similarly, hypertonic activation of ORE reporter was partially blocked by pharmacological inhibition of Fyn or by a dominant negative Fyn and was attenuated in Fyn-deficient cells. Importantly, inhibiting p38 in Fyn-deficient cells almost completely abolished the hypertonic induction of ORE reporter activity, indicating that p38 and Fyn are the major signaling pathways for the hypertonic activation of OREBP/TonEBP. Further we show that the transactivation domain of OREBP/TonEBP is the target of p38- and Fyn-mediated hypertonic activation. These results indicate a dual control in regulating the expression of the osmoprotective genes in mammalian cells.en_HK
dc.languageengen_HK
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_HK
dc.relation.ispartofJournal of Biological Chemistryen_HK
dc.rightsJournal of Biological Chemistry. Copyright © American Society for Biochemistry and Molecular Biology, Inc.en_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshCells, Cultureden_HK
dc.subject.meshDNA-Binding Proteins - metabolismen_HK
dc.subject.meshEnzyme Inhibitors - pharmacologyen_HK
dc.subject.meshGenes, Reporteren_HK
dc.subject.meshImidazoles - pharmacologyen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMitogen-Activated Protein Kinases - antagonists & inhibitors - metabolismen_HK
dc.subject.meshNFATC Transcription Factorsen_HK
dc.subject.meshOsmolar Concentrationen_HK
dc.subject.meshProto-Oncogene Proteins - antagonists & inhibitors - metabolismen_HK
dc.subject.meshProto-Oncogene Proteins c-fynen_HK
dc.subject.meshPyridines - pharmacologyen_HK
dc.subject.meshSignal Transductionen_HK
dc.subject.meshTranscription Factors - metabolismen_HK
dc.subject.meshTranscriptional Activationen_HK
dc.subject.meshp38 Mitogen-Activated Protein Kinasesen_HK
dc.titleFyn and p38 signaling are both required for maximal hypertonic activation of the osmotic response element-binding protein/tonicity-responsive enhancer-binding protein (OREBP/TonEBP)en_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0021-9258&volume=277&issue=48&spage=46085&epage=46092&date=2002&atitle=Fyn+and+p38+signaling+are+both+required+for+maximal+hypertonic+activation+of+the+osmotic+response+element-binding+protein/tonicity-responsive+enhancer-binding+protein+(OREBP/TonEBP)en_HK
dc.identifier.emailChung, SK: skchung@hkucc.hku.hken_HK
dc.identifier.emailChung, SSM: smchung@hkucc.hku.hken_HK
dc.identifier.authorityChung, SK=rp00381en_HK
dc.identifier.authorityChung, SSM=rp00376en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1074/jbc.M208138200en_HK
dc.identifier.pmid12359721-
dc.identifier.scopuseid_2-s2.0-0037195922en_HK
dc.identifier.hkuros76356en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0037195922&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume277en_HK
dc.identifier.issue48en_HK
dc.identifier.spage46085en_HK
dc.identifier.epage46092en_HK
dc.identifier.isiWOS:000179529300051-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridKo, BCB=7102833927en_HK
dc.identifier.scopusauthoridLam, AKM=7201848036en_HK
dc.identifier.scopusauthoridKapus, A=15042626200en_HK
dc.identifier.scopusauthoridFan, L=55185781300en_HK
dc.identifier.scopusauthoridChung, SK=7404292976en_HK
dc.identifier.scopusauthoridChung, SSM=14120761600en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats