Unequal contribution of Akt isoforms in the double-negative to double-positive thymocyte transition.

Unequal contribution of Akt isoforms in the double-negative to double-positive thymocyte transition. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Unequal contribution of Akt isoforms in the double-negative to double-positive thymocyte transition. Abstract Text:

Changchuin Mao,Esmerina G Tili,Marei Dose, Haks,Susan E Bear,Ioanna Maroulakou,Kyoji Horie,George A Gaitanaris,Vincenzo Fidanza,Thomas Ludwig,David L Wiest,Fotini Gounari,Philip N Tsichlis,

Pre-TCR signals regulate the transition of the double-negative (DN) 3 thymocytes to the DN4, and subsequently to the double-positive (DP) stage. In this study, we show that pre-TCR signals activate Akt and that pharmacological inhibition of the PI3K/Akt pathway, or combined ablation of Akt1 and Akt2, and to a lesser extent Akt1 and Akt3, interfere with the differentiation of DN3 and the accumulation of DP thymocytes. Combined ablation of Akt1 and Akt2 inhibits the proliferation of DN4 cells, while combined ablation of all Akt isoforms also inhibits the survival of all the DN thymocytes. Finally, the combined ablation of Akt1 and Akt2 inhibits the survival of DP thymocytes. Constitutively active Lck-Akt1 transgenes had the opposite effects. We conclude that, following their activation by pre-TCR signals, Akt1, Akt2, and, to a lesser extent, Akt3 promote the transition of DN thymocytes to the DP stage, in part by enhancing the proliferation and survival of cells undergoing beta-selection. Akt1 and Akt2 also contribute to the differentiation process by promoting the survival of the DP thymocytes.

Unequal contribution of Akt isoforms in the double-negative to double-positive thymocyte transition. Publishing Authors By Initials

C Mao,EG Tili,M Dose,MC Haks,SE Bear,I Maroulakou,K Horie,GA Gaitanaris,V Fidanza,T Ludwig,DL Wiest,F Gounari,PN Tsichlis,

For similar genetic structures: genome: genome components: genes: transgenes research abstracts see: genetic structures: genome: genome components: genes: transgenes research

PUBMED ID PMID:

MEDLINE DATE:

Unequal contribution of Akt isoforms in the double-negative to double-positive thymocyte transition. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of immunology (Baltimore, Md. : 1950)

VOLUME: 178

Page Numbers: 5443-53

Journal Abbreviation:

ISSN: 0022-1767

DAY: 1

MONTH: May

YEAR: 2007

Unequal contribution of Akt isoforms in the double-negative to double-positive thymocyte transition. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985117

Unequal contribution of Akt isoforms in the double-negative to double-positive thymocyte transition. Keywords Mesh Terms:

KEYWORDS: Transgenes

MESH TERMS: immunology

Chemical & Substance for Abstract: Unequal contribution of Akt isoforms in the double-negative to double-positive thymocyte transition. Information

Substance Name: Proto-Oncogene Proteins c-akt

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for Unequal contribution of Akt isoforms in the double-negative to double-positive thymocyte transition.

AFFILIATION: Molecular Oncology Research Institute, Tufts-New England Medical Center, 750 Washington Street, Boston, MA 02111, USA.

Country: United States

AGENCY: United States NCI

GRANT: T32 CA 009429

ACRONYM: CA

MEDLINETA: J Immunol

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Unequal contribution of Akt isoforms in the double-negative to double-positive thymocyte transition Related Publications

• Akt1 ablation inhibits, whereas Akt2 ablation accelerates, the development of mammary adenocarcinomas in mouse mammary tumor virus (MMTV)-ErbB2/neu and MMTV-polyoma middle T transgenic mice.
• Distinct roles of the three Akt isoforms in lactogenic differentiation and involution.
• Members of a family of JmjC domain-containing oncoproteins immortalize embryonic fibroblasts via a JmjC domain-dependent process.
• Proteinase-activated receptor-1-triggered activation of tumor progression locus-2 promotes actin cytoskeleton reorganization and cell migration.
• Tpl2 and ERK transduce antiproliferative T cell receptor signals and inhibit transformation of chronically stimulated T cells.
• Unequal contribution of Akt isoforms in the double-negative to double-positive thymocyte transition.