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Article: Activation of TORC1 transcriptional coactivator through MEKK1-induced phosphorylation

TitleActivation of TORC1 transcriptional coactivator through MEKK1-induced phosphorylation
Authors
Issue Date2008
PublisherAmerican Society for Cell Biology. The Journal's web site is located at http://www.molbiolcell.org/
Citation
Molecular Biology Of The Cell, 2008, v. 19 n. 11, p. 4750-4761 How to Cite?
AbstractCREB is a prototypic bZIP transcription factor and a master regulator of glucose metabolism, synaptic plasticity, cell growth, apoptosis, and tumorigenesis. Transducers of regulated CREB activity (TORCs) are essential transcriptional coactivators of CREB and an important point of regulation on which various signals converge. In this study, we report on the activation of TORC1 through MEKK1-mediated phosphorylation. MEKK1 potently activated TORC1, and this activation was independent of downstream effectors MEK1/MEK2, ERK2, JNK, p38, protein kinase A, and calcineurin. MEKK1 induced phosphorylation of TORC1 both in vivo and in vitro. Expression of the catalytic domain of MEKK1 alone in cultured mammalian cells sufficiently caused phosphorylation and subsequent activation of TORC1. MEKK1 physically interacted with TORC1 and stimulated its nuclear translocation. An activation domain responsive to MEKK1 stimulation was mapped to amino acids 431-650 of TORC1. As a physiological activator of CREB, interleukin 1α triggered MEKK1-dependent phosphorylation of TORC1 and its consequent recruitment to the cAMP response elements in the interleukin 8 promoter. Taken together, our findings suggest a new mechanism for regulated activation of TORC1 transcriptional coactivator and CREB signaling. © 2008 by The American Society for Cell Biology.
Persistent Identifierhttp://hdl.handle.net/10722/58210
ISSN
2015 Impact Factor: 4.037
2015 SCImago Journal Rankings: 3.665
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research CouncilHKU 7683/05M
HKU 7486/06M
HKU 7636/07M
HKU 7661/08M
HKU 1/06C
Center of National Institutes of HealthR01 TW06186-01
Association for International Cancer Research070424
Funding Information:

We thank Melanie Cobb, Silvio Gutkind, Naofumi Mukaida, Dennis Templeton, and Charles Vinson for gifts of plasmids and Tony Chin, Abel Chun, Raven Kok, James Ng, Vincent Tang, and Chi Ming Wong for critical reading of the manuscript. This work was supported by Hong Kong Research Council (HKU 7683/05M, HKU 7486/06M, HKU 7636/07M, HKU 7661/08M, and HKU 1/06C), Fogarty International Center of National Institutes of Health (R01 TW06186-01), and Association for International Cancer Research ( 070424) grants.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorSiu, YTen_HK
dc.contributor.authorChing, YPen_HK
dc.contributor.authorJin, DYen_HK
dc.date.accessioned2010-05-31T03:25:53Z-
dc.date.available2010-05-31T03:25:53Z-
dc.date.issued2008en_HK
dc.identifier.citationMolecular Biology Of The Cell, 2008, v. 19 n. 11, p. 4750-4761en_HK
dc.identifier.issn1059-1524en_HK
dc.identifier.urihttp://hdl.handle.net/10722/58210-
dc.description.abstractCREB is a prototypic bZIP transcription factor and a master regulator of glucose metabolism, synaptic plasticity, cell growth, apoptosis, and tumorigenesis. Transducers of regulated CREB activity (TORCs) are essential transcriptional coactivators of CREB and an important point of regulation on which various signals converge. In this study, we report on the activation of TORC1 through MEKK1-mediated phosphorylation. MEKK1 potently activated TORC1, and this activation was independent of downstream effectors MEK1/MEK2, ERK2, JNK, p38, protein kinase A, and calcineurin. MEKK1 induced phosphorylation of TORC1 both in vivo and in vitro. Expression of the catalytic domain of MEKK1 alone in cultured mammalian cells sufficiently caused phosphorylation and subsequent activation of TORC1. MEKK1 physically interacted with TORC1 and stimulated its nuclear translocation. An activation domain responsive to MEKK1 stimulation was mapped to amino acids 431-650 of TORC1. As a physiological activator of CREB, interleukin 1α triggered MEKK1-dependent phosphorylation of TORC1 and its consequent recruitment to the cAMP response elements in the interleukin 8 promoter. Taken together, our findings suggest a new mechanism for regulated activation of TORC1 transcriptional coactivator and CREB signaling. © 2008 by The American Society for Cell Biology.en_HK
dc.languageengen_HK
dc.publisherAmerican Society for Cell Biology. The Journal's web site is located at http://www.molbiolcell.org/en_HK
dc.relation.ispartofMolecular Biology of the Cellen_HK
dc.rightsMolecular Biology Of The Cell. Copyright © American Society for Cell Biology.en_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshCalcineurin - metabolismen_HK
dc.subject.meshCell Nucleus - metabolismen_HK
dc.subject.meshCyclic AMP-Dependent Protein Kinases - metabolismen_HK
dc.subject.meshExtracellular Signal-Regulated MAP Kinases - metabolismen_HK
dc.subject.meshHeLa Cellsen_HK
dc.subject.meshHumansen_HK
dc.subject.meshInterleukin-8 - geneticsen_HK
dc.subject.meshJNK Mitogen-Activated Protein Kinases - metabolismen_HK
dc.subject.meshMAP Kinase Kinase Kinase 1 - metabolismen_HK
dc.subject.meshPhosphorylationen_HK
dc.subject.meshPhosphothreonine - metabolismen_HK
dc.subject.meshPromoter Regions, Geneticen_HK
dc.subject.meshProtein Bindingen_HK
dc.subject.meshProtein Structure, Tertiaryen_HK
dc.subject.meshProtein Transporten_HK
dc.subject.meshTrans-Activators - metabolismen_HK
dc.subject.meshTranscription Factors - chemistry - genetics - metabolismen_HK
dc.subject.meshTranscription, Geneticen_HK
dc.subject.meshp38 Mitogen-Activated Protein Kinases - metabolismen_HK
dc.titleActivation of TORC1 transcriptional coactivator through MEKK1-induced phosphorylationen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1059-1524&volume=19&spage=4750&epage=61&date=2008&atitle=Activation+of+TORC1+transcriptional+coactivator+through+MEKK1-induced+phosphorylationen_HK
dc.identifier.emailChing, YP:ypching@hku.hken_HK
dc.identifier.emailJin, DY:dyjin@hkucc.hku.hken_HK
dc.identifier.authorityChing, YP=rp00469en_HK
dc.identifier.authorityJin, DY=rp00452en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1091/mbc.E08-04-0369en_HK
dc.identifier.pmid18784253-
dc.identifier.scopuseid_2-s2.0-58149286561en_HK
dc.identifier.hkuros154361en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-58149286561&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume19en_HK
dc.identifier.issue11en_HK
dc.identifier.spage4750en_HK
dc.identifier.epage4761en_HK
dc.identifier.isiWOS:000260472300019-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectMolecular pathology of liver cancer - a multidisciplinary study-
dc.relation.projectRoles for p21-activated protein kinase 3 in HTLV-I pathogenesis-
dc.relation.projectCharacterization of fusion oncoprotein FUS-CREB3L2 found in soft tissue sarcoma-
dc.identifier.scopusauthoridSiu, YT=8953557400en_HK
dc.identifier.scopusauthoridChing, YP=7005431277en_HK
dc.identifier.scopusauthoridJin, DY=7201973614en_HK

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