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Article: Protein kinase B regulates T lymphocyte survival, nuclear factor κB activation, and Bcl-X(L) levels in vivo

TitleProtein kinase B regulates T lymphocyte survival, nuclear factor κB activation, and Bcl-X(L) levels in vivo
Authors
Issue Date2000
PublisherRockefeller University Press. The Journal's web site is located at http://www.jem.org
Citation
Journal Of Experimental Medicine, 2000, v. 191 n. 10, p. 1721-1733 How to Cite?
AbstractThe serine/threonine kinase protein kinase B (PKB)/Akt mediates cell survival in a variety of systems. We have generated transgenic mice expressing a constitutively active form of PKB (gag-PKB) to examine the effects of PKB activity on T lymphocyte survival. Thymocytes and mature T cells overexpressing gag-PKB displayed increased active PKB, enhanced viability in culture, and resistance to a variety of apoptotic stimuli. PKB activity prolonged the survival of CD4+CD8+ double positive (DP) thymocytes in fetal thymic organ culture, but was unable to prevent antigen-induced clonal deletion of thymocytes expressing the major histocompatibility complex class I-restricted P14 T cell receptor (TCR). In mature T lymphocytes, PKB can be activated in response to TCR stimulation, and peptide-antigen-specific proliferation is enhanced in T cells expressing the gag-PKB transgene. Both thymocytes and T cells overexpressing gag-PKB displayed elevated levels of the antiapoptotic molecule Bcl-X(L). In addition, the activation of peripheral T cells led to enhanced nuclear factor (NF)-κB activation via accelerated degradation of the NF-κB inhibitory protein IκBα. Our data highlight a physiological role for PKB in promoting survival of DP thymocytes and mature T cells, and provide evidence for the direct association of three major survival molecules (PKB, Bcl-X(L), and NF-κB) in vivo in T lymphocytes.
Persistent Identifierhttp://hdl.handle.net/10722/132505
ISSN
2015 Impact Factor: 11.24
2015 SCImago Journal Rankings: 10.762
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorJones, RGen_HK
dc.contributor.authorParsons, Men_HK
dc.contributor.authorBonnard, Men_HK
dc.contributor.authorChan, VSFen_HK
dc.contributor.authorYeh, WCen_HK
dc.contributor.authorWoodgett, JRen_HK
dc.contributor.authorOhashi, PSen_HK
dc.date.accessioned2011-03-28T09:25:30Z-
dc.date.available2011-03-28T09:25:30Z-
dc.date.issued2000en_HK
dc.identifier.citationJournal Of Experimental Medicine, 2000, v. 191 n. 10, p. 1721-1733en_HK
dc.identifier.issn0022-1007en_HK
dc.identifier.urihttp://hdl.handle.net/10722/132505-
dc.description.abstractThe serine/threonine kinase protein kinase B (PKB)/Akt mediates cell survival in a variety of systems. We have generated transgenic mice expressing a constitutively active form of PKB (gag-PKB) to examine the effects of PKB activity on T lymphocyte survival. Thymocytes and mature T cells overexpressing gag-PKB displayed increased active PKB, enhanced viability in culture, and resistance to a variety of apoptotic stimuli. PKB activity prolonged the survival of CD4+CD8+ double positive (DP) thymocytes in fetal thymic organ culture, but was unable to prevent antigen-induced clonal deletion of thymocytes expressing the major histocompatibility complex class I-restricted P14 T cell receptor (TCR). In mature T lymphocytes, PKB can be activated in response to TCR stimulation, and peptide-antigen-specific proliferation is enhanced in T cells expressing the gag-PKB transgene. Both thymocytes and T cells overexpressing gag-PKB displayed elevated levels of the antiapoptotic molecule Bcl-X(L). In addition, the activation of peripheral T cells led to enhanced nuclear factor (NF)-κB activation via accelerated degradation of the NF-κB inhibitory protein IκBα. Our data highlight a physiological role for PKB in promoting survival of DP thymocytes and mature T cells, and provide evidence for the direct association of three major survival molecules (PKB, Bcl-X(L), and NF-κB) in vivo in T lymphocytes.en_HK
dc.languageengen_US
dc.publisherRockefeller University Press. The Journal's web site is located at http://www.jem.orgen_HK
dc.relation.ispartofJournal of Experimental Medicineen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshApoptosisen_HK
dc.subject.meshCell Survival - physiologyen_HK
dc.subject.meshDNA-Binding Proteins - metabolismen_HK
dc.subject.meshEnzyme Activationen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshGene Expressionen_HK
dc.subject.meshGenes, gagen_HK
dc.subject.meshHumansen_HK
dc.subject.meshI-kappa B Proteinsen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMice, Inbred C57BLen_HK
dc.subject.meshMice, Inbred CBAen_HK
dc.subject.meshMice, Transgenicen_HK
dc.subject.meshNF-kappa B - antagonists & inhibitors - metabolismen_HK
dc.subject.meshPregnancyen_HK
dc.subject.meshProtein-Serine-Threonine Kinasesen_HK
dc.subject.meshProto-Oncogene Proteins - genetics - metabolismen_HK
dc.subject.meshProto-Oncogene Proteins c-akten_HK
dc.subject.meshProto-Oncogene Proteins c-bcl-2 - metabolismen_HK
dc.subject.meshRNA, Messenger - genetics - metabolismen_HK
dc.subject.meshT-Lymphocytes - cytology - metabolismen_HK
dc.subject.meshbcl-X Proteinen_HK
dc.titleProtein kinase B regulates T lymphocyte survival, nuclear factor κB activation, and Bcl-X(L) levels in vivoen_HK
dc.typeArticleen_HK
dc.identifier.emailChan, VSF:sfvchan@hku.hken_HK
dc.identifier.authorityChan, VSF=rp01459en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1084/jem.191.10.1721en_HK
dc.identifier.pmid10811865-
dc.identifier.scopuseid_2-s2.0-0034658320en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0034658320&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume191en_HK
dc.identifier.issue10en_HK
dc.identifier.spage1721en_HK
dc.identifier.epage1733en_HK
dc.identifier.isiWOS:000087134100010-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridJones, RG=8085780700en_HK
dc.identifier.scopusauthoridParsons, M=35605732000en_HK
dc.identifier.scopusauthoridBonnard, M=7003593355en_HK
dc.identifier.scopusauthoridChan, VSF=35200370000en_HK
dc.identifier.scopusauthoridYeh, WC=7202860390en_HK
dc.identifier.scopusauthoridWoodgett, JR=7007172260en_HK
dc.identifier.scopusauthoridOhashi, PS=7006493798en_HK

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